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
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
May-2023 Volume 25 Issue 5

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
May-2023 Volume 25 Issue 5

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

  • Supplementary Files
    • Supplementary_Data.pdf
Article Open Access

Inhibition of phosphoinositide‑3 kinases γ/δ ameliorates pulmonary granuloma by rescuing Treg function in a sarcoidosis model

  • Authors:
    • Xian Zhang
    • Qianqian Dai
    • Jiajia Shan
    • Shiyun Zhang
    • Bin Zhang
    • Siyang Liu
    • Yixue Zhang
    • Ying Wang
    • Xiaojie Li
    • Xuguang Jin
    • Dongmei Liang
    • Jingjing Ding
    • Yong Wang
    • Yanting Wen
  • View Affiliations / Copyright

    Affiliations: State Key Laboratory of Pharmaceutical Biotechnology and Jiangsu Key Laboratory of Molecular Medicine, The Affiliated Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210093, P.R. China, Department of Respiratory Medicine and Jiangsu Key Laboratory of Molecular Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210003, P.R. China, State Key Laboratory of Analytical Chemistry for Life Science and Jiangsu Key Laboratory of Molecular Medicine, The Affiliated Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210093, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 225
    |
    Published online on: March 30, 2023
       https://doi.org/10.3892/etm.2023.11923
  • 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

Sarcoidosis is a multisystem inflammatory disease characterized by the development of Th1/Th17/regulatory T cells (Tregs)‑related non‑caseating granulomas. Phosphoinositide‑3 kinases δ/γ (PI3Kδ/γ) play an important role in the maintenance of effective immunity, especially for Tregs homeostasis and stability. In the present study, superoxide dismutase A (SodA) stimulation was used to establish the sarcoidosis mouse model. The second immune stimulus was accompanied by CAL‑101 (PI3Kδ inhibitor) or AS‑605240 (PI3Kδ/γ inhibitor) treatment. To detect the effect of the PI3Kδ/γ inhibitor on the morphology of pulmonary granuloma and the activation of the PI3K signaling pathway, hematoxylin and eosin staining and immunofluorescence and western blotting was used, respectively. Fluorescence‑activated cell sorting analysis and reverse transcription‑quantitative PCR were adopted to detect the effect of the PI3Kδ/γ inhibitor on the SodA‑induced sarcoidosis mouse model in respect to immune cell disorder and the function of Treg cells, with CD4+CD25‑ T cells and CD4+CD25+ T cells sorted by magnetic cell sorting. The results demonstrated that the inhibition of PI3Kδ/γ by transtracheal CAL‑101/AS‑605240 administration facilitated pulmonary granuloma formation. These therapeutic effects were associated with certain mechanisms, including suppressing the aberrantly activated PI3K/Akt signaling in both pulmonary granuloma and Tregs, particularly rescuing the suppressive function of Tregs. Notably, CAL‑101 was more effective in immune modulation compared with AS‑605240 and could overcome the aberrantly activated Akt in the lung and Tregs. These results suggest that PI3K/Akt signaling, especially the PI3Kδ subunit, can play a key role in optimal Tregs‑mediated protection against pulmonary sarcoidosis. Therefore, transtracheal usage of PI3Kδ/γ inhibitors is an attractive therapy that may be developed into a new immune‑therapeutic principle for sarcoidosis in the future.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Broos CE, van Nimwegen M, Hoogsteden HC, Hendriks RW, Kool M and van den Blink B: Granuloma formation in pulmonary sarcoidosis. Front Immunol. 4(437)2013.PubMed/NCBI View Article : Google Scholar

2 

Hunninghake GW, Costabel U, Ando M, Baughman R, Cordier JF, du Bois R, Eklund A, Kitaichi M, Lynch J, Rizzato G, et al: ATS/ERS/WASOG statement on sarcoidosis. American thoracic society/european respiratory society/world association of sarcoidosis and other granulomatous disorders. Sarcoidosis Vasc Diffuse Lung Dis. 16:149–173. 1999.PubMed/NCBI

3 

Oswald-Richter KA, Richmond BW, Braun NA, Isom J, Abraham S, Taylor TR, Drake JM, Culver DA, Wilkes DS and Drake WP: Reversal of global CD4+ subset dysfunction is associated with spontaneous clinical resolution of pulmonary sarcoidosis. J Immunol. 190:5446–5453. 2013.PubMed/NCBI View Article : Google Scholar

4 

Cinetto F and Agostini C: Advances in understanding the immunopathology of sarcoidosis and implications on therapy. Expert Rev Clin Immunol. 12:973–988. 2016.PubMed/NCBI View Article : Google Scholar

5 

Iannuzzi MC, Rybicki BA and Teirstein AS: Sarcoidosis. N Engl J Med. 357:2153–2165. 2007.PubMed/NCBI View Article : Google Scholar

6 

Gurram RK, Kujur W, Maurya SK and Agrewala JN: Caerulomycin A enhances transforming growth factor-β (TGF-β)-Smad3 protein signaling by suppressing interferon-γ (IFN-γ)-signal transducer and activator of transcription 1 (STAT1) protein signaling to expand regulatory T cells (Tregs). J Biol Chem. 289:17515–17528. 2014.PubMed/NCBI View Article : Google Scholar

7 

Ten Berge B, KleinJan A, Muskens F, Hammad H, Hoogsteden HC, Hendriks RW, Lambrecht BN and Van den Blink B: Evidence for local dendritic cell activation in pulmonary sarcoidosis. Respir Res. 13(33)2012.PubMed/NCBI View Article : Google Scholar

8 

Patterson KC and Chen ES: The pathogenesis of pulmonary sarcoidosis and implications for treatment. Chest. 153:1432–1442. 2018.PubMed/NCBI View Article : Google Scholar

9 

Miyara M, Amoura Z, Parizot C, Badoual C, Dorgham K, Trad S, Kambouchner M, Valeyre D, Chapelon-Abric C, Debré P, et al: The immune paradox of sarcoidosis and regulatory T cells. J Exp Med. 203:359–370. 2006.PubMed/NCBI View Article : Google Scholar

10 

Idali F, Wahlström J, Müller-Suur C, Eklund A and Grunewald J: Analysis of regulatory T cell associated forkhead box P3 expression in the lungs of patients with sarcoidosis. Clin Exp Immunol. 152:127–137. 2008.PubMed/NCBI View Article : Google Scholar

11 

Prasse A, Zissel G, Lützen N, Schupp J, Schmiedlin R, Gonzalez-Rey E, Rensing-Ehl A, Bacher G, Cavalli V, Bevec D, et al: Inhaled vasoactive intestinal peptide exerts immunoregulatory effects in sarcoidosis. Am J Respir Crit Care Med. 182:540–548. 2010.PubMed/NCBI View Article : Google Scholar

12 

Taflin C, Miyara M, Nochy D, Valeyre D, Naccache JM, Altare F, Salek-Peyron P, Badoual C, Bruneval P, Haroche J, et al: FoxP3+ regulatory T cells suppress early stages of granuloma formation but have little impact on sarcoidosis lesions. Am J Pathol. 174:497–508. 2009.PubMed/NCBI View Article : Google Scholar

13 

Rappl G, Pabst S, Riemann D, Schmidt A, Wickenhauser C, Schütte W, Hombach AA, Seliger B, Grohé C and Abken H: Regulatory T cells with reduced repressor capacities are extensively amplified in pulmonary sarcoid lesions and sustain granuloma formation. Clin Immunol. 140:71–83. 2011.PubMed/NCBI View Article : Google Scholar

14 

Ding J, Dai J, Cai H, Gao Q and Wen Y: Extensively disturbance of regulatory T cells-Th17 cells balance in stage II pulmonary sarcoidosis. Int J Med Sci. 14:1136–1142. 2017.PubMed/NCBI View Article : Google Scholar

15 

Zissel G and Müller-Quernheim J: Cellular players in the immunopathogenesis of sarcoidosis. Clin Chest Med. 36:549–560. 2015.PubMed/NCBI View Article : Google Scholar

16 

Zhang B, Zhao F, Mao H, Ma W, Zhang Y, Zhang X, Ding J, Gao Q and Wen Y: Interleukin 33 ameliorates disturbance of regulatory T cells in pulmonary sarcoidosis. Int Immunopharmacol. 64:208–216. 2018.PubMed/NCBI View Article : Google Scholar

17 

Zhang B, Dai Q, Jin X, Liang D, Li X, Lu H, Liu Y, Ding J, Gao Q and Wen Y: Phosphoinositide 3-kinase/protein kinase B inhibition restores regulatory T cell's function in pulmonary sarcoidosis. J Cell Physiol. 234:19911–19920. 2019.PubMed/NCBI View Article : Google Scholar

18 

Huynh A, DuPage M, Priyadharshini B, Sage PT, Quiros J, Borges CM, Townamchai N, Gerriets VA, Rathmell JC, Sharpe AH, et al: Control of PI(3) kinase in Treg cells maintains homeostasis and lineage stability. Nat Immunol. 16:188–196. 2015.PubMed/NCBI View Article : Google Scholar

19 

Greaves SA, Peterson JN, Strauch P, Torres RM and Pelanda R: Active PI3K abrogates central tolerance in high-avidity autoreactive B cells. J Exp Med. 216:1135–1153. 2019.PubMed/NCBI View Article : Google Scholar

20 

Swaisgood CM, Oswald-Richter K, Moeller SD, Klemenc JM, Ruple LM, Farver CF, Drake JM, Culver DA and Drake WP: Development of a sarcoidosis murine lung granuloma model using mycobacterium superoxide dismutase A peptide. Am J Respir Cell Mol Biol. 44:166–174. 2011.PubMed/NCBI View Article : Google Scholar

21 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar

22 

Abdel-Magid AF: Potential of PI3Kβ inhibitors in the treatment of cancer and other diseases. ACS Med Chem Lett. 8:778–780. 2017.PubMed/NCBI View Article : Google Scholar

23 

Rathinaswamy MK and Burke JE: Class I phosphoinositide 3-kinase (PI3K) regulatory subunits and their roles in signaling and disease. Adv Biol Regul. 75(100657)2020.PubMed/NCBI View Article : Google Scholar

24 

Scott WJ, Hentemann MF, Rowley RB, Bull CO, Jenkins S, Bullion AM, Johnson J, Redman A, Robbins AH, Esler W, et al: Discovery and SAR of novel 2,3-dihydroimidazo[1,2-c]quinazoline PI3K inhibitors: Identification of copanlisib (BAY 80-6946). ChemMedChem. 11:1517–1530. 2016.PubMed/NCBI View Article : Google Scholar

25 

Lannutti BJ, Meadows SA, Herman SE, Kashishian A, Steiner B, Johnson AJ, Byrd JC, Tyner JW, Loriaux MM, Deininger M, et al: CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability. Blood. 117:591–594. 2011.PubMed/NCBI View Article : Google Scholar

26 

Furet P, Guagnano V, Fairhurst RA, Imbach-Weese P, Bruce I, Knapp M, Fritsch C, Blasco F, Blanz J, Aichholz R, et al: Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation. Bioorg Med Chem Lett. 23:3741–3748. 2013.PubMed/NCBI View Article : Google Scholar

27 

Burris HA III, Flinn IW, Patel MR, Fenske TS, Deng C, Brander DM, Gutierrez M, Essell JH, Kuhn JG, Miskin HP, et al: Umbralisib, a novel PI3Kδ and casein kinase-1ε inhibitor, in relapsed or refractory chronic lymphocytic leukaemia and lymphoma: An open-label, phase 1, dose-escalation, first-in-human study. Lancet Oncol. 19:486–496. 2018.PubMed/NCBI View Article : Google Scholar

28 

Patel RK and Mohan C: PI3K/AKT signaling and systemic autoimmunity. Immunol Res. 31:47–55. 2005.PubMed/NCBI View Article : Google Scholar

29 

Adefemi F, Fruman DA and Marshall AJ: A case for phosphoinositide 3-kinase-targeted therapy for infectious disease. J Immunol. 205:3237–3245. 2020.PubMed/NCBI View Article : Google Scholar

30 

Franks SE, Getahun A and Cambier JC: A precision B cell-targeted therapeutic approach to autoimmunity caused by phosphatidylinositol 3-kinase pathway dysregulation. J Immunol. 202:3381–3393. 2019.PubMed/NCBI View Article : Google Scholar

31 

Winkler DG, Faia KL, DiNitto JP, Ali JA, White KF, Brophy EE, Pink MM, Proctor JL, Lussier J, Martin CM, et al: PI3K-δ and PI3K-γ inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models. Chem Biol. 20:1364–1374. 2013.PubMed/NCBI View Article : Google Scholar

32 

Steinbach EC, Kobayashi T, Russo SM, Sheikh SZ, Gipson GR, Kennedy ST, Uno JK, Mishima Y, Borst LB, Liu B, et al: Innate PI3K p110δ regulates Th1/Th17 development and microbiota-dependent colitis. J Immunol. 192:3958–3968. 2014.PubMed/NCBI View Article : Google Scholar

33 

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.PubMed/NCBI View Article : Google Scholar

34 

Horak F, Puri KD, Steiner BH, Holes L, Xing G, Zieglmayer P, Zieglmayer R, Lemell P and Yu A: Randomized phase 1 study of the phosphatidylinositol 3-kinase δ inhibitor idelalisib in patients with allergic rhinitis. J Allergy Clin Immunol. 137:1733–1741. 2016.PubMed/NCBI View Article : Google Scholar

35 

Perry MWD, Bjorhall K, Bold P, Brűlls M, Börjesson U, Carlsson J, Chang HA, Chen Y, Eriksson A, Fihn BM, et al: Discovery of AZD8154, a dual PI3Kγδ inhibitor for the treatment of asthma. J Med Chem. 64:8053–8075. 2021.PubMed/NCBI View Article : Google Scholar

36 

Stark AK, Davenport ECM, Patton DT, Scudamore CL, Vanhaesebroeck B, Veldhoen M, Garden OA and Okkenhaug K: Loss of phosphatidylinositol 3-kinase activity in regulatory T cells leads to neuronal inflammation. J Immunol. 205:78–89. 2020.PubMed/NCBI View Article : Google Scholar

37 

Li H, Park D, Abdul-Muneer PM, Xu B, Wang H, Xing B, Wu D and Li S: PI3Kγ inhibition alleviates symptoms and increases axon number in experimental autoimmune encephalomyelitis mice. Neuroscience. 253:89–99. 2013.PubMed/NCBI View Article : Google Scholar

38 

Zillikens H, Kasprick A, Osterloh C, Gross N, Radziewitz M, Hass C, Hartmann V, Behnen-Härer M, Ernst N, Boch K, et al: Topical application of the PI3Kβ-selective small molecule inhibitor TGX-221 Is an effective treatment option for experimental epidermolysis bullosa acquisita. Front Med (Lausanne). 8(713312)2021.PubMed/NCBI View Article : Google Scholar

39 

Hawkins PT and Stephens LR: PI3K signalling in inflammation. Biochim Biophys Acta. 1851:882–897. 2015.PubMed/NCBI View Article : Google Scholar

40 

Liu Y, Qiu L, Wang Y, Aimurola H, Zhao Y, Li S and Xu Z: The circulating Treg/Th17 cell ratio is correlated with relapse and treatment response in pulmonary sarcoidosis patients after corticosteroid withdrawal. PLoS One. 11(e0148207)2016.PubMed/NCBI View Article : Google Scholar

41 

Uehara M, McGrath MM, Ohori S, Solhjou Z, Banouni N, Routray S, Evans C, DiNitto JP, Elkhal A, Turka LA, et al: Regulation of T cell alloimmunity by PI3Kγ and PI3Kδ. Nat Commun. 8(951)2017.PubMed/NCBI View Article : Google Scholar

42 

Gamper CJ and Powell JD: All PI3Kinase signaling is not mTOR: Dissecting mTOR-dependent and independent signaling pathways in T cells. Front Immunol. 3(312)2012.PubMed/NCBI View Article : Google Scholar

43 

Lim EL and Okkenhaug K: Phosphoinositide 3-kinase δ is a regulatory T-cell target in cancer immunotherapy. Immunology. 157:210–218. 2019.PubMed/NCBI View Article : Google Scholar

44 

Vanhaesebroeck B, Perry MWD, Brown JR, André F and Okkenhaug K: PI3K inhibitors are finally coming of age. Nat Rev Drug Discov. 20:741–769. 2021.PubMed/NCBI View Article : Google Scholar

45 

Randis TM, Puri KD, Zhou H and Diacovo TG: Role of PI3Kdelta and PI3Kgamma in inflammatory arthritis and tissue localization of neutrophils. Eur J Immunol. 38:1215–1224. 2008.PubMed/NCBI View Article : Google Scholar

46 

Williams O, Houseman BT, Kunkel EJ, Aizenstein B, Hoffman R, Knight ZA and Shokat KM: Discovery of dual inhibitors of the immune cell PI3Ks p110delta and p110gamma: A prototype for new anti-inflammatory drugs. Chem Biol. 17:123–134. 2010.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhang X, Dai Q, Shan J, Zhang S, Zhang B, Liu S, Zhang Y, Wang Y, Li X, Jin X, Jin X, et al: Inhibition of phosphoinositide‑3 kinases γ/δ ameliorates pulmonary granuloma by rescuing Treg function in a sarcoidosis model. Exp Ther Med 25: 225, 2023.
APA
Zhang, X., Dai, Q., Shan, J., Zhang, S., Zhang, B., Liu, S. ... Wen, Y. (2023). Inhibition of phosphoinositide‑3 kinases γ/δ ameliorates pulmonary granuloma by rescuing Treg function in a sarcoidosis model. Experimental and Therapeutic Medicine, 25, 225. https://doi.org/10.3892/etm.2023.11923
MLA
Zhang, X., Dai, Q., Shan, J., Zhang, S., Zhang, B., Liu, S., Zhang, Y., Wang, Y., Li, X., Jin, X., Liang, D., Ding, J., Wang, Y., Wen, Y."Inhibition of phosphoinositide‑3 kinases γ/δ ameliorates pulmonary granuloma by rescuing Treg function in a sarcoidosis model". Experimental and Therapeutic Medicine 25.5 (2023): 225.
Chicago
Zhang, X., Dai, Q., Shan, J., Zhang, S., Zhang, B., Liu, S., Zhang, Y., Wang, Y., Li, X., Jin, X., Liang, D., Ding, J., Wang, Y., Wen, Y."Inhibition of phosphoinositide‑3 kinases γ/δ ameliorates pulmonary granuloma by rescuing Treg function in a sarcoidosis model". Experimental and Therapeutic Medicine 25, no. 5 (2023): 225. https://doi.org/10.3892/etm.2023.11923
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang X, Dai Q, Shan J, Zhang S, Zhang B, Liu S, Zhang Y, Wang Y, Li X, Jin X, Jin X, et al: Inhibition of phosphoinositide‑3 kinases γ/δ ameliorates pulmonary granuloma by rescuing Treg function in a sarcoidosis model. Exp Ther Med 25: 225, 2023.
APA
Zhang, X., Dai, Q., Shan, J., Zhang, S., Zhang, B., Liu, S. ... Wen, Y. (2023). Inhibition of phosphoinositide‑3 kinases γ/δ ameliorates pulmonary granuloma by rescuing Treg function in a sarcoidosis model. Experimental and Therapeutic Medicine, 25, 225. https://doi.org/10.3892/etm.2023.11923
MLA
Zhang, X., Dai, Q., Shan, J., Zhang, S., Zhang, B., Liu, S., Zhang, Y., Wang, Y., Li, X., Jin, X., Liang, D., Ding, J., Wang, Y., Wen, Y."Inhibition of phosphoinositide‑3 kinases γ/δ ameliorates pulmonary granuloma by rescuing Treg function in a sarcoidosis model". Experimental and Therapeutic Medicine 25.5 (2023): 225.
Chicago
Zhang, X., Dai, Q., Shan, J., Zhang, S., Zhang, B., Liu, S., Zhang, Y., Wang, Y., Li, X., Jin, X., Liang, D., Ding, J., Wang, Y., Wen, Y."Inhibition of phosphoinositide‑3 kinases γ/δ ameliorates pulmonary granuloma by rescuing Treg function in a sarcoidosis model". Experimental and Therapeutic Medicine 25, no. 5 (2023): 225. https://doi.org/10.3892/etm.2023.11923
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