Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
April-2026 Volume 57 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
April-2026 Volume 57 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review Open Access

mTOR signaling pathway in primary Sjögren's syndrome: Pathogenesis and potential therapeutic targets (Review)

  • Authors:
    • Rongxiu Huo
    • Yanting Yang
    • Chengcheng Wei
    • Yang Yang
    • Danli Meng
    • Jinying Lin
    • Xinxiang Huang
  • View Affiliations / Copyright

    Affiliations: Department of Rheumatology and Immunology, Guangxi Academy of Medical Sciences, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi 530016, P.R. China
    Copyright: © Huo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 104
    |
    Published online on: February 25, 2026
       https://doi.org/10.3892/ijmm.2026.5775
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:


Abstract

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disorder that can progress from asymptomatic glandular involvement to systemic manifestations affecting multiple organs, thereby imposing a notable economic burden on both patients and society. The pathogenesis of pSS is complex and involves multifactorial interactions between genetic, environmental and immune components. Although pSS is a common rheumatic disease, current therapeutic approaches primarily focus on symptom management and no curative treatment is available. Therefore, it is key to identify novel and effective therapeutic strategies for affected individuals. The mTOR signaling pathway is a key regulatory pathway in numerous types of cell, playing a crucial role in immune regulation, inflammation and autophagy. Activation of this pathway can promote inflammation by inducing immune dysregulation, thereby contributing to the pathogenesis of pSS. Conversely, inhibition of the mTOR signaling pathway mitigates these pathological processes and may help alleviate disease severity. Thus, the mTOR signaling pathway represents a promising therapeutic target for pSS. The present review aimed to elucidate the role and underlying mechanisms of the mTOR signaling pathway in pSS and provide a theoretical foundation for developing targeted therapeutic interventions.
View Figures

Figure 1

mTOR signaling pathway components and
related functions. Growth factors, cytokines and mitogen-activated
RTKs attach to the plasma membrane by recruiting PI3K, which
catalyzes PIP2 to PIP3 conversion. PTEN can inhibit this process.
PIP3 promotes AKT activation via the activity of mTORC1 and mTORC2.
AKT activation induces the phosphorylation of the downstream
substrate TSC2 and inhibits its activity, promotes the activation
of mTORC1, activates the downstream S6RP and initiates eukaryotic
protein translation. Activation of 4E-BP1 enhances the release of
eIF4E. mTOR signaling promotes cell cycle progression, cell
proliferation, survival and protein synthesis. RTK, receptor
tyrosine kinase; PI3K, phosphatidylinositol 3-kinase; PIP2,
phosphatidylinositol 4,5-bisphosphate; PIP3, phosphatidylinositol
3,4,5-triphosphate; TSC, tuberous sclerosis; 4E-BP, eIF4E-binding
protein; mLST8, mammalian lethal with SEC thirteen 8; Rictor,
rapamycin-insensitive companion of mTOR; S6KP, ribosomal S6 kinase
polypeptide; Raptor, regulatory-associated protein of mTOR.

Figure 2

Effects of mTOR signaling pathway
activation on immune cells. mTOR signaling is activated in immune
cells under the action of cytokines and growth factors. DCs secrete
type I IFN and differentiate into monocytes. Monocytes primarily
differentiate into M1 cells, leading to an imbalance between M1 and
M2 macrophages and the release of cytokines, which causes
immunopathology. The activation of the mTOR signaling pathway in T
cells increases the expression of Tbet, GATA3 and RORγt and
decreases the expression of FOXP3, promoting the differentiation of
primordial T cells into Th1, Th2, Th17 cells and CTL, inhibiting
the differentiation into Treg and Tfh cells and causing an
imbalance between Th17 and Treg cells. Th17 cells secrete
pro-inflammatory cytokines, such as TNF-α, IL-6, IL-17 and IFN-γ.
The activation of the mTOR signaling pathway enhances BAFF
stimulation, thereby leading to the uncontrolled proliferation of B
cells and the production of excessive autoantibodies. This immune
imbalance is associated with autoimmune diseases. DC, dendritic
cell; Tbet, T-box transcription factor TBX21; GATA3, GATA binding
protein 3; RORγt, retinoic acid receptor-related orphan receptor
γt; FOXP3, forkhead box P3; Th, thelper; CTL, cytotoxic T
lymphocyte; Treg, regulatory T; Tfh, T follicular helper; TNF,
tumor necrosis factor; BAFF, B cell activating factor.

Figure 3

Potential mechanisms of mTOR
signaling in the pathogenesis of pSS. In pSS, the levels of
inflammatory cytokines and growth factors increase. After binding
receptors on the surface of immune cells, These inflammatory
cytokines and growth factors activate the mTOR signaling pathway of
these cells, promoting the proliferation and differentiation of
immune cells and their infiltration into the glands. For example,
DCs secrete a large amount of type I IFN. In addition to secreting
a large amount of type I IFN, the infiltration of M1 macrophages
can also produce inflammatory cytokines (TNF-α, IL-6, IL-12) and
induce T cells to differentiate into Th1 cells. When T cells are
activated by the mTOR signaling pathway, they differentiate into
Th1, Th2 and Th17 cells and CTL, and infiltrate glandular
epithelial cells. Th1 cells secrete pro-inflammatory cytokines such
as IFN-γ and TNF-α, while Th17 cells secrete IL-17 and induce the
production of IL-6, TNF-α and IL-1β. Th2 cells secrete IL-4,
promoting the activation of B cells. Under the action of type I
IFN, BAFF is activated, which leads to the activation of B cells
and the production of excessive autoantibodies. These antibodies
bind glandular epithelial cells, activating CTL and secreting IFN-γ
and TNF-α. Under the influence of immune cells and inflammatory
cytokines, inflammation of the glands and blood vessels occurs,
leading to an increase in vascular permeability. Under the action
of chemokines, DCs, B and T cells and monocytes in peripheral blood
migrate to the glands. In this state of immune imbalance, the tight
junction structure of glandular epithelial cells is disrupted,
leading to progressive damage to the glandular structure and
secretory dysfunction, which develops into pSS. DC, dendritic cell;
Th, thelper; CTL, cytotoxic T lymphocyte; Treg, regulatory T; TNF,
tumor necrosis factor; BAFF, B cell activating factor; Ab,
autoantibody; SGEC, salivary gland epithelial cell; pSS, primary
Sjögren's syndrome; SG, salivary gland.
View References

1 

Manfrè V, Chatzis LG, Cafaro G, Fonzetti S, Calvacchi S, Fulvio G, Navarro Garcia IC, La Rocca G, Ferro F, Perricone C, et al: Sjögren's syndrome: One year in review 2022. Clin Exp Rheumatol. 40:2211–2224. 2022.

2 

Stefanski AL, Tomiak C, Pleyer U, Dietrich T, Burmester GR and Dörner T: The diagnosis and treatment of Sjögren's syndrome. Dtsch Arztebl Int. 114:354–361. 2017.PubMed/NCBI

3 

Koh JH, Park Y, Lee J, Jeon H, Moon SJ, Kim YH, Min JK, Park SH and Kwok SK: Long-term outcome of interstitial lung disease in patients with primary Sjögren's syndrome: A retrospective observational study. Korean J Intern Med. 40:148–159. 2025. View Article : Google Scholar :

4 

Lessard CJ, Li H, Adrianto I, Ice JA, Rasmussen A, Grundahl KM, Kelly JA, Dozmorov MG, Miceli-Richard C, Bowman S, et al: Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren's syndrome. Nat Genet. 45:1284–1292. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Liu Z and Chu A: Sjögren's syndrome and viral infections. Rheumatol Ther. 8:1051–1059. 2021. View Article : Google Scholar : PubMed/NCBI

6 

Kapsogeorgou EK and Tzioufas AG: Interaction of human salivary gland epithelial cells with B lymphocytes: Implications in the pathogenesis of Sjögren's syndrome. Mediterr J Rheumatol. 31:424–426. 2020. View Article : Google Scholar

7 

Haacke EA, Bootsma H, Spijkervet FKL, Visser A, Vissink A, Kluin PM and Kroese FGM: FcRL4+ B-cells in salivary glands of primary Sjögren's syndrome patients. J Autoimmun. 81:90–98. 2017. View Article : Google Scholar : PubMed/NCBI

8 

Tanaka Y, Sotome T, Inoue A, Mukozu T, Kuwabara T, Mikami T, Kowhi-Shigematsu T and Kondo M: SATB1 conditional knockout results in Sjögren's syndrome in mice. J Immunol. 199:4016–4022. 2017. View Article : Google Scholar : PubMed/NCBI

9 

van Blokland SC, van Helden-Meeuwsen CG, Wierenga-Wolf AF, Drexhage HA, Hooijkaas H, van de Merwe JP and Versnel MA: Two different types of sialoadenitis in the NOD- and MRL/lpr mouse models for Sjögren's syndrome: A differential role for dendritic cells in the initiation of sialoadenitis? Lab Invest. 80:575–585. 2000. View Article : Google Scholar : PubMed/NCBI

10 

Tian Y, Yang H, Liu N, Li Y and Chen J: Advances in pathogenesis of Sjögren's syndrome. J Immunol Res. 2021:59282322021. View Article : Google Scholar

11 

Ramos-Casals M, Brito-Zerón P, Bombardieri S, Bootsma H, De Vita S, Dörner T, Fisher BA, Gottenberg JE, Hernandez-Molina G, Kocher A, et al: EULAR recommendations for the management of Sjögren's syndrome with topical and systemic therapies. Ann Rheum Dis. 79:3–18. 2020. View Article : Google Scholar

12 

Dorjsembe B, Joo H, Nho C, Ham J and Kim JC: Aruncus dioicus var. kamtschaticus extract ameliorates psoriasis-like skin inflammation via Akt/mTOR and JAK2/STAT3 signaling pathways in a murine model. Nutrients. 14:50942022. View Article : Google Scholar : PubMed/NCBI

13 

Roy T, Banang-Mbeumi S, Boateng ST, Ruiz EM, Chamcheu RN, Kang L, King JA, Walker AL, Nagalo BM, Kousoulas KG, et al: Dual targeting of mTOR/IL-17A and autophagy by fisetin alleviates psoriasis-like skin inflammation. Front Immunol. 13:10758042023. View Article : Google Scholar : PubMed/NCBI

14 

Shah M, Edman MC, Janga SR, Shi P, Dhandhukia J, Liu S, Louie SG, Rodgers K, Mackay JA and Hamm-Alvarez SF: A rapamycin-binding protein polymer nanoparticle shows potent therapeutic activity in suppressing autoimmune dacryoadenitis in a mouse model of Sjögren's syndrome. J Control Release. 171:269–279. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Shan J, Jin H and Xu Y: T cell metabolism: A new perspective on Th17/treg cell imbalance in systemic lupus erythematosus. Front Immunol. 11:10272020. View Article : Google Scholar : PubMed/NCBI

16 

Heitman J, Movva NR and Hall MN: Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast. Science. 253:905–909. 1991. View Article : Google Scholar : PubMed/NCBI

17 

Sabatini DM, Erdjument-Bromage H, Lui M, Tempst P and Snyder SH: RAFT1: A mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs. Cell. 78:35–43. 1994. View Article : Google Scholar : PubMed/NCBI

18 

Mita MM, Mita A and Rowinsky EK: Mammalian target of rapamycin: A new molecular target for breast cancer. Clin Breast Cancer. 4:126–137. 2003. View Article : Google Scholar : PubMed/NCBI

19 

Keith CT and Schreiber SL: PIK-related kinases: DNA repair, recombination, and cell cycle checkpoints. Science. 270:50–51. 1995. View Article : Google Scholar : PubMed/NCBI

20 

Yang M, Lu Y, Piao W and Jin H: The translational regulation in mTOR pathway. Biomolecules. 12:8022022. View Article : Google Scholar : PubMed/NCBI

21 

Kim YC and Guan KL: mTOR: A pharmacologic target for autophagy regulation. J Clin Invest. 125:25–32. 2015. View Article : Google Scholar : PubMed/NCBI

22 

Sun Y, Wang H, Qu T, Luo J, An P, Ren F, Luo Y and Li Y: mTORC2: A multifaceted regulator of autophagy. Cell Commun Signal. 21:42023. View Article : Google Scholar : PubMed/NCBI

23 

Zoncu R, Efeyan A and Sabatini DM: mTOR: From growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol. 12:21–35. 2011. View Article : Google Scholar

24 

Nunnery SE and Mayer IA: Targeting the PI3K/AKT/mTOR pathway in hormone-positive breast cancer. Drugs. 80:1685–1697. 2020. View Article : Google Scholar : PubMed/NCBI

25 

Yilmaz OH and Morrison SJ: The PI-3kinase pathway in hematopoietic stem cells and leukemia-initiating cells: A mechanistic difference between normal and cancer stem cells. Blood Cells Mol Dis. 41:73–76. 2008. View Article : Google Scholar : PubMed/NCBI

26 

Korets SB, Czok S, Blank SV, Curtin JP and Schneider RJ: Targeting the mTOR/4E-BP pathway in endometrial cancer. Clin Cancer Res. 17:7518–7528. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Magnuson B, Ekim B and Fingar DC: Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks. Biochem J. 441:1–21. 2012. View Article : Google Scholar

28 

Alves CL and Ditzel HJ: Drugging the PI3K/AKT/mTOR pathway in ER+ breast cancer. Int J Mol Sci. 24:45222023. View Article : Google Scholar : PubMed/NCBI

29 

Grabiner BC, Nardi V, Birsoy K, Possemato R, Shen K, Sinha S, Jordan A, Beck AH and Sabatini DM: A diverse array of cancer-associated MTOR mutations are hyperactivating and can predict rapamycin sensitivity. Cancer Discov. 4:554–563. 2014. View Article : Google Scholar : PubMed/NCBI

30 

Marnett LJ: Lipid peroxidation-DNA damage by malondialdehyde. Mutat Res. 424:83–95. 1999.PubMed/NCBI

31 

Lai ZW, Kelly R, Winans T, Marchena I, Shadakshari A, Yu J, Dawood M, Garcia R, Tily H, Francis L, et al: Sirolimus in patients with clinically active systemic lupus erythematosus resistant to, or intolerant of, conventional medications: A single-arm, open-label, phase 1/2 trial. Lancet. 391:1186–1196. 2018. View Article : Google Scholar : PubMed/NCBI

32 

Shortman K and Liu YJ: Mouse and human dendritic cell subtypes. Nat Rev Immunol. 2:151–161. 2002. View Article : Google Scholar : PubMed/NCBI

33 

Sukhbaatar N, Hengstschläger M and Weichhart T: mTOR-mediated regulation of dendritic cell differentiation and function. Trends Immunol. 37:778–789. 2016. View Article : Google Scholar : PubMed/NCBI

34 

Sathaliyawala T, O'Gorman WE, Greter M, Bogunovic M, Konjufca V, Hou ZE, Nolan GP, Miller MJ, Merad M and Reizis B: Mammalian target of rapamycin controls dendritic cell development downstream of Flt3 ligand signaling. Immunity. 33:597–606. 2010. View Article : Google Scholar : PubMed/NCBI

35 

van de Laar L, Buitenhuis M, Wensveen FM, Janssen HL, Coffer PJ and Woltman AM: Human CD34-derived myeloid dendritic cell development requires intact phosphatidylinositol 3-kinase-protein kinase B-mammalian target of rapamycin signaling. J Immunol. 184:6600–6611. 2010. View Article : Google Scholar : PubMed/NCBI

36 

Schmitz F, Heit A, Dreher S, Eisenächer K, Mages J, Haas T, Krug A, Janssen KP, Kirschning CJ and Wagner H: Mammalian target of rapamycin (mTOR) orchestrates the defense program of innate immune cells. Eur J Immunol. 38:2981–2992. 2008. View Article : Google Scholar : PubMed/NCBI

37 

Haidinger M, Poglitsch M, Geyeregger R, Kasturi S, Zeyda M, Zlabinger GJ, Pulendran B, Hörl WH, Säemann MD and Weichhart T: A versatile role of mammalian target of rapamycin in human dendritic cell function and differentiation. J Immunol. 185:3919–3931. 2010. View Article : Google Scholar : PubMed/NCBI

38 

Katholnig K, Linke M, Pham H, Hengstschläger M and Weichhart T: Immune responses of macrophages and dendritic cells regulated by mTOR signalling. Biochem Soc Trans. 41:927–933. 2013. View Article : Google Scholar : PubMed/NCBI

39 

Auffray C, Sieweke MH and Geissmann F: Blood monocytes: Development, heterogeneity, and relationship with dendritic cells. Annu Rev Immunol. 27:669–692. 2009. View Article : Google Scholar : PubMed/NCBI

40 

Shi C and Pamer EG: Monocyte recruitment during infection and inflammation. Nat Rev Immunol. 11:762–774. 2011. View Article : Google Scholar : PubMed/NCBI

41 

Italiani P and Boraschi D: From monocytes to M1/M2 macrophages: Phenotypical vs. functional differentiation. Front Immunol. 5:5142014. View Article : Google Scholar : PubMed/NCBI

42 

Shalova IN, Lim JY, Chittezhath M, Zinkernagel AS, Beasley F, Hernández-Jiménez E, Toledano V, Cubillos-Zapata C, Rapisarda A, Chen J, et al: Human monocytes undergo functional re-programming during sepsis mediated by hypoxia-inducible factor-1α. Immunity. 42:484–498. 2015. View Article : Google Scholar : PubMed/NCBI

43 

Chung YH, Kim DH and Lee WW: Monosodium urate crystal-induced pro-interleukin-1β production is post-transcriptionally regulated via the p38 signaling pathway in human monocytes. Sci Rep. 6:345332016. View Article : Google Scholar

44 

Weichhart T, Costantino G, Poglitsch M, Rosner M, Zeyda M, Stuhlmeier KM, Kolbe T, Stulnig TM, Hörl WH, Hengstschläger M, et al: The TSC-mTOR signaling pathway regulates the innate inflammatory response. Immunity. 29:565–577. 2008. View Article : Google Scholar : PubMed/NCBI

45 

Rauh MJ, Ho V, Pereira C, Sham A, Sly LM, Lam V, Huxham L, Minchinton AI, Mui A and Krystal G: SHIP represses the generation of alternatively activated macrophages. Immunity. 23:361–374. 2005. View Article : Google Scholar : PubMed/NCBI

46 

Araki K, Ellebedy AH and Ahmed R: TOR in the immune system. Curr Opin Cell Biol. 23:707–715. 2011. View Article : Google Scholar : PubMed/NCBI

47 

Linke M, Pham HT, Katholnig K, Schnöller T, Miller A, Demel F, Schütz B, Rosner M, Kovacic B, Sukhbaatar N, et al: Chronic signaling via the metabolic checkpoint kinase mTORC1 induces macrophage granuloma formation and marks sarcoidosis progression. Nat Immunol. 18:293–302. 2017. View Article : Google Scholar : PubMed/NCBI

48 

Panwar V, Singh A, Bhatt M, Tonk RK, Azizov S, Raza AS, Sengupta S, Kumar D and Garg M: Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease. Signal Transduct Target Ther. 8:3752023. View Article : Google Scholar : PubMed/NCBI

49 

Wang R, Dillon CP, Shi LZ, Milasta S, Carter R, Finkelstein D, McCormick LL, Fitzgerald P, Chi H, Munger J and Green DR: The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation. Immunity. 35:871–882. 2011. View Article : Google Scholar : PubMed/NCBI

50 

Kusaba H, Ghosh P, Derin R, Buchholz M, Sasaki C, Madara K and Longo DL: Interleukin-12-induced interferon-gamma production by human peripheral blood T cells is regulated by mammalian target of rapamycin (mTOR). J Biol Chem. 280:1037–1043. 2005. View Article : Google Scholar

51 

Waickman AT and Powell JD: mTOR, metabolism, and the regulation of T-cell differentiation and function. Immunol Rev. 249:43–58. 2012. View Article : Google Scholar : PubMed/NCBI

52 

Mafi S, Mansoori B, Taeb S, Sadeghi H, Abbasi R, Cho WC and Rostamzadeh D: mTOR-mediated regulation of immune responses in cancer and tumor microenvironment. Front Immunol. 12:7741032022. View Article : Google Scholar : PubMed/NCBI

53 

Delgoffe GM, Kole TP, Cotter RJ and Powell JD: Enhanced interaction between Hsp90 and raptor regulates mTOR signaling upon T cell activation. Mol Immunol. 46:2694–2698. 2009. View Article : Google Scholar : PubMed/NCBI

54 

Delgoffe GM, Kole TP, Zheng Y, Zarek PE, Matthews KL, Xiao B, Worley PF, Kozma SC and Powell JD: The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment. Immunity. 30:832–844. 2009. View Article : Google Scholar : PubMed/NCBI

55 

Lee WH, Kim GE, Hong KJ, Kim HS and Lee GR: Insulin receptor substrate 1 signaling inhibits Foxp3 expression and suppressive functions in Treg cells through the mTORC1 pathway. Int J Mol Sci. 24:25512023. View Article : Google Scholar : PubMed/NCBI

56 

Pollizzi KN, Patel CH, Sun IH, Oh MH, Waickman AT, Wen J, Delgoffe GM and Powell JD: mTORC1 and mTORC2 selectively regulate CD8+ T cell differentiation. J Clin Invest. 125:2090–2108. 2015. View Article : Google Scholar : PubMed/NCBI

57 

Zeng H and Chi H: mTOR signaling in the differentiation and function of regulatory and effector T cells. Curr Opin Immunol. 46:103–111. 2017. View Article : Google Scholar : PubMed/NCBI

58 

Tangye SG, Nguyen T, Deenick EK, Bryant VL and Ma CS: Inborn errors of human B cell development, differentiation, and function. J Exp Med. 220:e202211052023. View Article : Google Scholar : PubMed/NCBI

59 

Staniek J and Rizzi M: Signaling activation and modulation in extrafollicular B cell responses. Immunol Rev. 330:e700042025. View Article : Google Scholar : PubMed/NCBI

60 

Jones DD, Gaudette BT, Wilmore JR, Chernova I, Bortnick A, Weiss BM and Allman D: mTOR has distinct functions in generating versus sustaining humoral immunity. J Clin Invest. 126:4250–4261. 2026. View Article : Google Scholar

61 

Tsui C, Martinez-Martin N, Gaya M, Maldonado P, Llorian M, Legrave NM, Rossi M, MacRae JI, Cameron AJ, Parker PJ, et al: Protein kinase C-β dictates B cell fate by regulating mitochondrial remodeling, metabolic reprogramming, and heme biosynthesis. Immunity. 48:1144–1159.e5. 2018. View Article : Google Scholar

62 

Benhamron S, Pattanayak SP, Berger M and Tirosh B: mTOR activation promotes plasma cell differentiation and bypasses XBP-1 for immunoglobulin secretion. Mol Cell Biol. 35:153–166. 2015. View Article : Google Scholar

63 

Zhang S, Readinger JA, DuBois W, Janka-Junttila M, Robinson R, Pruitt M, Bliskovsky V, Wu JZ, Sakakibara K, Patel J, et al: Constitutive reductions in mTOR alter cell size, immune cell development, and antibody production. Blood. 117:1228–1238. 2011. View Article : Google Scholar

64 

Iwata TN, Ramírez JA, Tsang M, Park H, Margineantu DH, Hockenbery DM and Iritani BM: Conditional disruption of raptor reveals an essential role for mTORC1 in B cell development, survival, and metabolism. J Immunol. 197:2250–2260. 2016. View Article : Google Scholar : PubMed/NCBI

65 

Gaudette BT, Jones DD, Bortnick A, Argon Y and Allman D: mTORC1 coordinates an immediate unfolded protein response-related transcriptome in activated B cells preceding antibody secretion. Nat Commun. 11:7232020. View Article : Google Scholar : PubMed/NCBI

66 

Zeng Q, Qin S, Zhang H, Liu B, Qin J, Wang X, Zhang R, Liu C, Dong X, Zhang S, et al: Rapamycin attenuates BAFF-extended proliferation and survival via disruption of mTORC1/2 signaling in normal and neoplastic B-lymphoid cells. J Cell Physiol. 233:516–529. 2018. View Article : Google Scholar

67 

Qin B, Wang J, Yang Z, Yang M, Ma N, Huang F and Zhong R: Epidemiology of primary Sjögren's syndrome: A systematic review and meta-analysis. Ann Rheum Dis. 74:1983–1989. 2015. View Article : Google Scholar

68 

Mavragani CP and Moutsopoulos HM: The geoepidemiology of Sjögren's syndrome. Autoimmun Rev. 9:A305–A310. 2010. View Article : Google Scholar

69 

Baldini C, Pepe P, Quartuccio L, Priori R, Bartoloni E, Alunno A, Gattamelata A, Maset M, Modesti M, Tavoni A, et al: Primary Sjogren's syndrome as a multi-organ disease: impact of the serological profile on the clinical presentation of the disease in a large cohort of Italian patients. Rheumatology (Oxford). 53:839–844. 2014. View Article : Google Scholar

70 

Brito-Zerón P, Theander E, Baldini C, Seror R, Retamozo S, Quartuccio L, Bootsma H, Bowman SJ, Dörner T, Gottenberg JE, et al: Early diagnosis of primary Sjögren's syndrome: EULAR-SS task force clinical recommendations. Expert Rev Clin Immunol. 12:137–156. 2016. View Article : Google Scholar

71 

Weng MY, Huang YT, Liu MF and Lu TH: Incidence and mortality of treated primary Sjogren's syndrome in Taiwan: A population-based study. J Rheumatol. 38:706–708. 2011. View Article : Google Scholar : PubMed/NCBI

72 

Maldini C, Seror R, Fain O, Dhote R, Amoura Z, De Bandt M, Delassus JL, Falgarone G, Guillevin L, Le Guern V, et al: Epidemiology of primary Sjögren's syndrome in a French multiracial/multiethnic area. Arthritis Care Res (Hoboken). 66:454–463. 2014. View Article : Google Scholar

73 

Brito-Zerón P, Acar-Denizli N, Zeher M, Rasmussen A, Seror R, Theander E, Li X, Baldini C, Gottenberg JE, Danda D, et al: Influence of geolocation and ethnicity on the phenotypic expression of primary Sjögren's syndrome at diagnosis in 8310 patients: A cross-sectional study from the big data Sjögren project consortium. Ann Rheum Dis. 76:1042–1050. 2017. View Article : Google Scholar

74 

Singh AG, Singh S and Matteson EL: Rate, risk factors and causes of mortality in patients with Sjögren's syndrome: A systematic review and meta-analysis of cohort studies. Rheumatology (Oxford). 55:450–460. 2016.

75 

Ren Y, Cui G and Gao Y: Research progress on inflammatory mechanism of primary Sjögren syndrome. Zhejiang Da Xue Xue Bao Yi Xue Ban. 50:783–794. 2021.

76 

Mavragani CP and Moutsopoulos HM: Sjögren's syndrome: Old and new therapeutic targets. J Autoimmun. 110:1023642020. View Article : Google Scholar

77 

Cai Y, Sun R, Wang R, Ren JG, Zhang W, Zhao YF and Zhao JH: The activation of Akt/mTOR pathway by bleomycin in Epithelial-to-mesenchymal transition of human submandibular gland cells: A treatment mechanism of bleomycin for mucoceles of the salivary glands. Biomed Pharmacother. 90:109–115. 2017. View Article : Google Scholar : PubMed/NCBI

78 

Soypaçacı Z, Gümüş ZZ, Çakaloğlu F, Özmen M, Solmaz D, Gücenmez S, Gercik Ö and Akar S: Role of the mTOR pathway in minor salivary gland changes in Sjogren's syndrome and systemic sclerosis. Arthritis Res Ther. 20:1702018. View Article : Google Scholar

79 

Assinder SJ, Dong Q, Kovacevic Z and Richardson DR: The TGF-beta, PI3K/Akt and PTEN pathways: Established and proposed biochemical integration in prostate cancer. Biochem J. 417:411–421. 2009. View Article : Google Scholar

80 

Blokland SLM, Hillen MR, Wichers CGK, Zimmermann M, Kruize AA, Radstake TRDJ, Broen JCA and van Roon JAG: Increased mTORC1 activation in salivary gland B cells and T cells from patients with Sjögren's syndrome: mTOR inhibition as a novel therapeutic strategy to halt immunopathology? RMD Open. 5:e0007012019. View Article : Google Scholar

81 

Zeng P, Jiang Z, Huang Z, Huang Y, Xu H, Chen C and Ma W: PI3K/AKT/mTOR signaling pathway is downregulated by runzaoling (RZL) in Sjögren's syndrome. Mediators Inflamm. 2022:72361182022. View Article : Google Scholar

82 

Shields CA, McCalmon M, Ibrahim T, White DL, Williams JM, LaMarca B and Cornelius DC: Placental ischemia-stimulated T-helper 17 cells induce preeclampsia-associated cytolytic natural killer cells during pregnancy. Am J Physiol Regul Integr Comp Physiol. 315:R336–R343. 2018. View Article : Google Scholar : PubMed/NCBI

83 

Wang W, Sung N, Gilman-Sachs A and Kwak-Kim J: T helper (Th) cell profiles in pregnancy and recurrent pregnancy losses: Th1/Th2/Th9/Th17/Th22/Tfh cells. Front Immunol. 11:20252020. View Article : Google Scholar : PubMed/NCBI

84 

Veldhoen M: Interleukin 17 is a chief orchestrator of immunity. Nat Immunol. 18:612–621. 2017. View Article : Google Scholar : PubMed/NCBI

85 

Barone F, Nayar S, Campos J, Cloake T, Withers DR, Toellner KM, Zhang Y, Fouser L, Fisher B, Bowman S, et al: IL-22 regulates lymphoid chemokine production and assembly of tertiary lymphoid organs. Proc Natl Acad Sci USA. 112:11024–11029. 2015. View Article : Google Scholar : PubMed/NCBI

86 

Gao L, Dong Y, Lin R, Meng Y, Wu F and Jia L: The imbalance of Treg/Th17 cells induced by perinatal bisphenol A exposure is associated with activation of the PI3K/Akt/mTOR signaling pathway in male offspring mice. Food Chem Toxicol. 137:1111772020. View Article : Google Scholar

87 

Singh N and Cohen PL: The T cell in Sjogren's syndrome: Force majeure, not spectateur. J Autoimmun. 39:229–233. 2012. View Article : Google Scholar : PubMed/NCBI

88 

Qi W, Tian J, Wang G, Yan Y, Wang T, Wei Y, Wang Z, Zhang G, Zhang Y and Wang J: Advances in cellular and molecular pathways of salivary gland damage in Sjögren's syndrome. Front Immunol. 15:14051262024. View Article : Google Scholar

89 

Sisto M, Lisi S, Lofrumento DD, Frassanito MA, Cucci L, D'Amore S, Mitolo V and D'Amore M: Induction of TNF-alpha-converting enzyme-ectodomain shedding by pathogenic autoantibodies. Int Immunol. 21:1341–1349. 2009. View Article : Google Scholar : PubMed/NCBI

90 

Crotty S: A brief history of T cell help to B cells. Nat Rev Immunol. 15:185–189. 2015. View Article : Google Scholar : PubMed/NCBI

91 

Nocturne G and Mariette X: B cells in the pathogenesis of primary Sjögren syndrome. Nat Rev Rheumatol. 14:133–145. 2018. View Article : Google Scholar : PubMed/NCBI

92 

Zhao J, Kubo S, Nakayamada S, Shimajiri S, Zhang X, Yamaoka K and Tanaka Y: Association of plasmacytoid dendritic cells with B cell infiltration in minor salivary glands in patients with Sjögren's syndrome. Mod Rheumatol. 26:716–724. 2016. View Article : Google Scholar

93 

Baturone R, Soto MJ, Márquez M, Macías I, de Oca MM, Medina F, Chozas N, García-Pérez S and Girón-González JA: Health-related quality of life in patients with primary Sjögren's syndrome: Relationship with serum levels of proinflammatory cytokines. Scand J Rheumatol. 38:386–389. 2009. View Article : Google Scholar

94 

Zong Y, Yang Y, Zhao J, Li L, Luo D, Hu J, Gao Y, Wei L, Li N and Jiang L: Characterisation of macrophage infiltration and polarisation based on integrated transcriptomic and histological analyses in Primary Sjögren's syndrome. Front Immunol. 14:12921462023. View Article : Google Scholar

95 

Lu X, Li N, Zhao L, Guo D, Yi H, Yang L, Liu X, Sun D, Nian H and Wei R: Human umbilical cord mesenchymal stem cells alleviate ongoing autoimmune dacryoadenitis in rabbits via polarizing macrophages into an anti-inflammatory phenotype. Exp Eye Res. 191:1079052020. View Article : Google Scholar : PubMed/NCBI

96 

Caprio M, Newfell BG, la Sala A, Baur W, Fabbri A, Rosano G, Mendelsohn ME and Jaffe IZ: Functional mineralocorticoid receptors in human vascular endothelial cells regulate intercellular adhesion molecule-1 expression and promote leukocyte adhesion. Circ Res. 102:1359–1367. 2008. View Article : Google Scholar : PubMed/NCBI

97 

Błochowiak KJ, Olewicz-Gawlik A, Trzybulska D, Nowak-Gabryel M, Kocięcki J, Witmanowski H and Sokalski J: Serum ICAM-1, VCAM-1 and E-selectin levels in patients with primary and secondary Sjögren's syndrome. Adv Clin Exp Med. 26:835–842. 2017. View Article : Google Scholar

98 

Silver N, Proctor GB, Arno M and Carpenter GH: Activation of mTOR coincides with autophagy during ligation-induced atrophy in the rat submandibular gland. Cell Death Dis. 1:e142010. View Article : Google Scholar : PubMed/NCBI

99 

Maleki-Fischbach M, Kastsianok L, Koslow M and Chan ED: Manifestations and management of Sjögren's disease. Arthritis Res Ther. 26:432024. View Article : Google Scholar

100 

Price EJ, Rauz S, Tappuni AR, Sutcliffe N, Hackett KL, Barone F, Granata G, Ng WF, Fisher BA, Bombardieri M, et al: The British society for rheumatology guideline for the management of adults with primary Sjögren's syndrome. Rheumatology (Oxford). 56:e24–e48. 2017. View Article : Google Scholar

101 

Negrini S, Emmi G, Greco M, Borro M, Sardanelli F, Murdaca G, Indiveri F and Puppo F: Sjögren's syndrome: A systemic autoimmune disease. Clin Exp Med. 22:9–25. 2022. View Article : Google Scholar :

102 

Yura Y and Hamada M: Outline of salivary gland pathogenesis of Sjögren's syndrome and current therapeutic approaches. Int J Mol Sci. 24:111792023. View Article : Google Scholar

103 

Su X, Yu H, Lei Q, Chen X, Tong Y, Zhang Z, Yang W, Guo Y and Lin L: Systemic lupus erythematosus: Pathogenesis and targeted therapy. Mol Biomed. 5:542024. View Article : Google Scholar : PubMed/NCBI

104 

Shao Y, Fu J, Zhan T, Ye L and Yu C: Fangchinoline inhibited proliferation of neoplastic B-lymphoid cells and alleviated Sjögren's syndrome-like responses in NOD/Ltj mice via the Akt/mTOR pathway. Curr Mol Pharmacol. 15:969–979. 2022. View Article : Google Scholar

105 

Zhou KG, Huang YB, Zhu ZW, Jiang M, Jin LJ, Guan Q, Tian LL and Zhang JX: Mesencephalic astrocyte-derived neurotrophic factor inhibits neuroinflammation through autophagy-mediated α-synuclein degradation. Arch Gerontol Geriatr. 131:1057382025. View Article : Google Scholar

106 

Cheng D, Zhou T, Liu H, Li L, Xuan Y, Huang L, Liu Y, Zhang X, Wei W and Wu H: MANF inhibits Sjögren's syndrome salivary gland epithelial cell apoptosis and antigen expression of Ro52/SSA through endoplasmic reticulum stress/autophagy pathway. Int Immunopharmacol. 122:1105822023. View Article : Google Scholar

107 

Lyu T, Jiang H, Zeng L, Liu S, He C, Luo C, Qiao L, Zhao Y and Chen H: Iguratimod suppresses Tfh cell differentiation in primary Sjögren's syndrome patients through inhibiting Akt/mTOR/STAT3 signaling. Arthritis Res Ther. 25:1522023. View Article : Google Scholar

108 

Ju Y, Edman MC, Guo H, Janga SR, Peddi S, Louie SG, Junge JA, MacKay JA and Hamm-Alvarez SF: Intralacrimal sustained delivery of rapamycin shows therapeutic effects without systemic toxicity in a mouse model of autoimmune dacryoadenitis characteristic of Sjögren's syndrome. Biomacromolecules. 22:1102–1114. 2021. View Article : Google Scholar

109 

Kim J, Kim YS and Park SH: Metformin as a treatment strategy for Sjögren's syndrome. Int J Mol Sci. 22:72312021. View Article : Google Scholar

110 

Kim JW, Kim SM, Park JS, Hwang SH, Choi J, Jung KA, Ryu JG, Lee SY, Kwok SK, Cho ML and Park SH: Metformin improves salivary gland inflammation and hypofunction in murine Sjögren's syndrome. Arthritis Res Ther. 21:1362019. View Article : Google Scholar

111 

Zhang S and Li J, Nong X, Zhan Y, Xu J, Zhao D, Ma C, Wang Y, Li Y, Li Z and Li J: Artesunate combined with metformin ameliorate on diabetes-induced xerostomia by mitigating superior salivatory nucleus and salivary glands injury in type 2 diabetic rats via the PI3K/AKT pathway. Front Pharmacol. 12:7746742021. View Article : Google Scholar

112 

Nayar S, Campos J, Smith CG, Iannizzotto V, Gardner DH, Colafrancesco S, Pipi E, Kollert F, Hunter KJ, Brewer C, et al: Phosphatidylinositol 3-kinase delta pathway: A novel therapeutic target for Sjögren's syndrome. Ann Rheum Dis. 78:249–260. 2019. View Article : Google Scholar :

113 

Scuron MD, Fay BL, Connell AJ, Oliver J and Smith PA: The PI3Kδ inhibitor parsaclisib ameliorates pathology and reduces autoantibody formation in preclinical models of systemic lupus erythematosus and Sjӧgren's syndrome. Int Immunopharmacol. 98:1079042021. View Article : Google Scholar

114 

Kaneko Y, Fukahori H, Yamagami K, Kawashima T, Ito M, Akamatsu M, Marui T, Kato K, Takahashi F and Morokata T: Effects of AS2819899, a novel selective PI3Kδ inhibitor, in a NZB/W F1 mouse lupus-like nephritis model. Int Immunopharmacol. 87:1067642020. View Article : Google Scholar

115 

Yamaguchi J, Isnard P, Robil N, de la Grange P, Hoguin C, Schmitt A, Hummel A, Megret J, Goudin N, Luka M, et al: PIK3CA inhibition in models of proliferative glomerulonephritis and lupus nephritis. J Clin Invest. 134:e1764022024. View Article : Google Scholar : PubMed/NCBI

116 

Juarez M, Diaz N, Johnston GI, Nayar S, Payne A, Helmer E, Cain D, Williams P, Devauchelle-Pensec V, Fisher BA, et al: A phase 2 randomized, double-blind, placebo-controlled, proof-of-concept study of oral seletalisib in primary Sjögren's syndrome. Rheumatology (Oxford). 60:1364–1375. 2021. View Article : Google Scholar

117 

Wu C, Wang Q, Xu D, Li M and Zeng X: Sirolimus for patients with connective tissue disease-related refractory thrombocytopenia: A single-arm, open-label clinical trial. Rheumatology (Oxford). 60:2629–2634. 2021. View Article : Google Scholar

118 

Du H, Su W, Su J, Hu J, Wu D, Long W and Zhu J: Sirolimus for the treatment of patients with refractory connective tissue disease-related thrombocytopenia: A pilot study. Rheumatology (Oxford). 63:79–84. 2024. View Article : Google Scholar

119 

Li X, Su L, Sun X, Li X, Tian Z, Liao Q, Sun W and Zhao Y: Effect of sirolimus on connective tissue disease related refractory thrombocytopenia: Clinical efficacy and immunomodulatory mechanism. Postepy Dermatol Alergol. 42:494–501. 2025.PubMed/NCBI

120 

Jiang N, Li M, Zhang H, Duan X, Li X, Fang Y, Li H, Yang P, Luo H, Wang Y, et al: Sirolimus versus tacrolimus for systemic lupus erythematosus treatment: Results from a real-world CSTAR cohort study. Lupus Sci Med. 9:e0006172022. View Article : Google Scholar : PubMed/NCBI

121 

Bai W, Peng L, Gui Y, Chen Y, Duan X, Li X, Zhang H, Huo Y, Xu J, Yang P, et al: Sirolimus versus mycophenolate mofetil for the treatment of lupus nephritis: Results from a real-world CSTAR cohort study. Rheumatol Immunol Res. 6:80–89. 2025. View Article : Google Scholar : PubMed/NCBI

122 

Mariette X, Barone F, Baldini C, Bootsma H, Clark KL, De Vita S, Gardner DH, Henderson RB, Herdman M, Lerang K, et al: A randomized, phase II study of sequential belimumab and rituximab in primary Sjögren's syndrome. JCI Insight. 7:e1630302022. View Article : Google Scholar

123 

Moysidou GS, Garantziotis P, Sentis G, Nikoleri D, Malissovas N, Nikoloudaki M, Stergioti EM, Polia S, Paschalidis N, Filia A, et al: Molecular basis for the disease-modifying effects of belimumab in systemic lupus erythematosus and molecular predictors of early response: Blood transcriptome analysis implicates the innate immunity and DNA damage response pathways. Ann Rheum Dis. 84:262–273. 2025. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Huo R, Yang Y, Wei C, Yang Y, Meng D, Lin J and Huang X: mTOR signaling pathway in primary Sjögren's syndrome: Pathogenesis and potential therapeutic targets (Review). Int J Mol Med 57: 104, 2026.
APA
Huo, R., Yang, Y., Wei, C., Yang, Y., Meng, D., Lin, J., & Huang, X. (2026). mTOR signaling pathway in primary Sjögren's syndrome: Pathogenesis and potential therapeutic targets (Review). International Journal of Molecular Medicine, 57, 104. https://doi.org/10.3892/ijmm.2026.5775
MLA
Huo, R., Yang, Y., Wei, C., Yang, Y., Meng, D., Lin, J., Huang, X."mTOR signaling pathway in primary Sjögren's syndrome: Pathogenesis and potential therapeutic targets (Review)". International Journal of Molecular Medicine 57.4 (2026): 104.
Chicago
Huo, R., Yang, Y., Wei, C., Yang, Y., Meng, D., Lin, J., Huang, X."mTOR signaling pathway in primary Sjögren's syndrome: Pathogenesis and potential therapeutic targets (Review)". International Journal of Molecular Medicine 57, no. 4 (2026): 104. https://doi.org/10.3892/ijmm.2026.5775
Copy and paste a formatted citation
x
Spandidos Publications style
Huo R, Yang Y, Wei C, Yang Y, Meng D, Lin J and Huang X: mTOR signaling pathway in primary Sjögren's syndrome: Pathogenesis and potential therapeutic targets (Review). Int J Mol Med 57: 104, 2026.
APA
Huo, R., Yang, Y., Wei, C., Yang, Y., Meng, D., Lin, J., & Huang, X. (2026). mTOR signaling pathway in primary Sjögren's syndrome: Pathogenesis and potential therapeutic targets (Review). International Journal of Molecular Medicine, 57, 104. https://doi.org/10.3892/ijmm.2026.5775
MLA
Huo, R., Yang, Y., Wei, C., Yang, Y., Meng, D., Lin, J., Huang, X."mTOR signaling pathway in primary Sjögren's syndrome: Pathogenesis and potential therapeutic targets (Review)". International Journal of Molecular Medicine 57.4 (2026): 104.
Chicago
Huo, R., Yang, Y., Wei, C., Yang, Y., Meng, D., Lin, J., Huang, X."mTOR signaling pathway in primary Sjögren's syndrome: Pathogenesis and potential therapeutic targets (Review)". International Journal of Molecular Medicine 57, no. 4 (2026): 104. https://doi.org/10.3892/ijmm.2026.5775
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team