IL‑35 may maintain homeostasis of the immune microenvironment in periodontitis

Jin,Ying; Liu,Dixin; Lin,Xiaoping

doi:10.3892/etm.2017.5255

IL‑35 may maintain homeostasis of the immune microenvironment in periodontitis

Authors:
- Ying Jin
- Dixin Liu
- Xiaoping Lin
View Affiliations

Affiliations: Department of Stomatology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
Published online on: October 3, 2017 https://doi.org/10.3892/etm.2017.5255
Pages: 5605-5610

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

T lymphocyte cells, including regulatory T (Treg) and T helper 17 cells, have important roles in the human periodontium. However, the basis for Treg cytokine expression in various compartments of the periodontium remains unclear. The aim of the present study was to investigate the expression of interleukin (IL)‑35 in the peripheral blood mononuclear cells (PBMCs) and periodontal tissues of patients with chronic periodontitis (CP), with a view to understanding its role in this disease, and ultimately providing improved treatments. Peripheral blood, periodontal tissues and gingival crevicular fluids (GCFs) were collected from patients with CP or impacted teeth, the latter serving as healthy controls. The expression levels of IL‑35 subunit mRNAs in PBMCs and periodontal tissues were determined using reverse transcription‑quantitative polymerase chain reaction, while the IL‑35 protein expression in GCFs and sera was quantified by ELISA. The relative expression of IL‑35 subunit mRNAs in the affected tissues of patients with CP was significantly higher compared with that in samples from healthy controls (P<0.05). The mean concentration of IL‑35 protein in the GCFs and sera of patients with periodontitis was also significantly higher compared with that in samples from healthy controls (P<0.001). IL‑35 protein and periodontal clinical indicators were negatively correlated. It was hypothesized that the increased level of IL‑35 plays a protective role in periodontal disease by maintaining immune system homeostasis and dampening the inflammatory response, and highlights IL‑35 as a potential new therapy for the treatment of periodontitis.

View Figures

View References

1	Di Benedetto A, Gigante I, Colucci S and Grano M: Periodontal disease: Linking the primary inflammation to bone loss. Clin Dev Immunol. 2013:5037542013. View Article : Google Scholar : PubMed/NCBI
2	Mendes L, Azevedo NF, Felino A and Pinto MG: Relationship between invasion of the periodontium by periodontal pathogens and periodontal disease: A systematic review. Virulence. 6:208–215. 2015. View Article : Google Scholar : PubMed/NCBI
3	Yucel-Lindberg T and Båge T: Inflammatory mediators in the pathogenesis of periodontitis. Expert Rev Mol Med. 15:e72013. View Article : Google Scholar : PubMed/NCBI
4	Gonzales JR: T- and B-cell subsets in periodontitis. Periodontol 2000. 69:181–200. 2015. View Article : Google Scholar : PubMed/NCBI
5	Campbell L, Millhouse E, Malcolm J and Culshaw S: T cells, teeth and tissue destruction - what do T cells do in periodontal disease? Mol Oral Microbiol. 31:445–456. 2016. View Article : Google Scholar : PubMed/NCBI
6	Hernández M, Dutzan N, García-Sesnich J, Abusleme L, Dezerega A, Silva N, González FE, Vernal R, Sorsa T and Gamonal J: Host-pathogen interactions in progressive chronic periodontitis. J Dent Res. 90:1164–1170. 2011. View Article : Google Scholar : PubMed/NCBI
7	Collison LW, Workman CJ, Kuo TT, Boyd K, Wang Y, Vignali KM, Cross R, Sehy D, Blumberg RS and Vignali DA: The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature. 450:566–569. 2007. View Article : Google Scholar : PubMed/NCBI
8	Shevach EM, DiPaolo RA, Andersson J, Zhao DM, Stephens GL and Thornton AM: The lifestyle of naturally occurring CD4⁺ CD25⁺ Foxp3⁺ regulatory T cells. Immunol Rev. 212:60–73. 2006. View Article : Google Scholar : PubMed/NCBI
9	Xystrakis E, Boswell SE and Hawrylowicz CM: T regulatory cells and the control of allergic disease. Expert Opin Biol Ther. 6:121–133. 2006. View Article : Google Scholar : PubMed/NCBI
10	Coombes JL, Robinson NJ, Maloy KJ, Uhlig HH and Powrie F: Regulatory T cells and intestinal homeostasis. Immunol Rev. 204:184–194. 2005. View Article : Google Scholar : PubMed/NCBI
11	Annacker O, Pimenta-Araujo R, Burlen-Defranoux O and Bandeira A: On the ontogeny and physiology of regulatory T cells. Immunol Rev. 182:5–17. 2001. View Article : Google Scholar : PubMed/NCBI
12	Wang L, Wang J, Jin Y, Gao H and Lin X: Oral administration of all-trans retinoic acid suppresses experimental periodontitis by modulating the Th17/Treg imbalance. J Periodontol. 85:740–750. 2014. View Article : Google Scholar : PubMed/NCBI
13	Collison LW and Vignali DA: Interleukin-35: Odd one out or part of the family? Immunol Rev. 226:248–262. 2008. View Article : Google Scholar : PubMed/NCBI
14	Choi J, Leung PS, Bowlus C and Gershwin ME: IL-35 and Autoimmunity: A comprehensive perspective. Clin Rev Allergy Immunol. 49:327–332. 2015. View Article : Google Scholar : PubMed/NCBI
15	Niedbala W, Wei XQ, Cai B, Hueber AJ, Leung BP, McInnes IB and Liew FY: IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cells and suppression of Th17 cells. Eur J Immunol. 37:3021–3029. 2007. View Article : Google Scholar : PubMed/NCBI
16	Hu Y, Dong C, Yue Y and Xiong S: In vivo delivery of interleukin-35 relieves coxsackievirus-B3-induced viral myocarditis by inhibiting Th17 cells. Arch Virol. 159:2411–2419. 2014. View Article : Google Scholar : PubMed/NCBI
17	Terayama H, Yoshimoto T, Hirai S, Naito M, Qu N, Hatayama N, Hayashi S, Mitobe K, Furusawa J, Mizoguchi I, et al: Contribution of IL-12/IL-35 common subunit p35 to maintaining the testicular immune privilege. PLoS One. 9:e961202014. View Article : Google Scholar : PubMed/NCBI
18	Guan SY, Leng RX, Khan MI, Qureshi H, Li XP, Ye DQ and Pan HF: Interleukin-35: A potential therapeutic agent for autoimmune diseases. Inflammation. 40:303–310. 2017. View Article : Google Scholar : PubMed/NCBI
19	Wu X, Offenbacher S, Lόpez NJ, Chen D, Wang HY, Rogus J, Zhou J, Beck J, Jiang S, Bao X, et al: Association of interleukin-1 gene variations with moderate to severe chronic periodontitis in multiple ethnicities. J Periodontal Res. 50:52–61. 2015. View Article : Google Scholar : PubMed/NCBI
20	Dutzan N, Gamonal J, Silva A, Sanz M and Vernal R: Over-expression of forkhead box P3 and its association with receptor activator of nuclear factor-kappa B ligand, interleukin (IL)-17, IL-10 and transforming growth factor-beta during the progression of chronic periodontitis. J Clin Periodontol. 36:396–403. 2009. View Article : Google Scholar : PubMed/NCBI
21	Joosten SA and Ottenhoff TH: Human CD4 and CD8 regulatory T cells in infectious diseases and vaccination. Hum Immunol. 69:760–770. 2008. View Article : Google Scholar : PubMed/NCBI
22	Ohlrich EJ, Cullinan MP and Seymour GJ: The immunopathogenesis of periodontal disease. Aust Dent J. 54 Suppl 1:S2–S10. 2009. View Article : Google Scholar : PubMed/NCBI
23	Alroqi FJ and Chatila TA: T regulatory cell biology in health and disease. Curr Allergy Asthma Rep. 16:272016. View Article : Google Scholar : PubMed/NCBI
24	Collison LW, Chaturvedi V, Henderson AL, Giacomin PR, Guy C, Bankoti J, Finkelstein D, Forbes K, Workman CJ, Brown SA, et al: IL-35-mediated induction of a potent regulatory T cell population. Nat Immunol. 11:1093–1101. 2010. View Article : Google Scholar : PubMed/NCBI
25	Collison LW, Pillai MR, Chaturvedi V and Vignali DA: Regulatory T cell suppression is potentiated by target T cells in a cell contact, IL-35- and IL-10-dependent manner. J Immunol. 182:6121–6128. 2009. View Article : Google Scholar : PubMed/NCBI
26	Clavel G, Thiolat A and Boissier MC: Interleukin newcomers creating new numbers in rheumatology: IL-34 to IL-38. Joint Bone Spine. 80:449–453. 2013. View Article : Google Scholar : PubMed/NCBI
27	Ma J and Xie LZ: Eukaryotic expression and biological activity of human interleukin-35. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 35:618–622. 2013.(In Chinese). PubMed/NCBI
28	Zhang YL, Zhou XY, Guo XY and Tu JW: Association between serum interleukin-35 levels and severity of acute pancreatitis. Int J Clin Exp Med. 8:7430–7434. 2015.PubMed/NCBI
29	Egwuagu CE, Yu CR, Sun L and Wang R: Interleukin 35: Critical regulator of immunity and lymphocyte-mediated diseases. Cytokine Growth Factor Rev. 26:587–593. 2015. View Article : Google Scholar : PubMed/NCBI
30	Liu JQ, Liu Z, Zhang X, Shi Y, Talebian F, Carl JW Jr, Yu C, Shi FD, Whitacre CC, Trgovcich J and Bai XF: Increased Th17 and regulatory T cell responses in EBV-induced gene 3-deficient mice lead to marginally enhanced development of autoimmune encephalomyelitis. J Immunol. 188:3099–3106. 2012. View Article : Google Scholar : PubMed/NCBI
31	Tirotta E, Duncker P, Oak J, Klaus S, Tsukamoto MR, Gov L and Lane TE: Epstein-Barr virus-induced gene 3 negatively regulates neuroinflammation and T cell activation following coronavirus-induced encephalomyelitis. J Neuroimmunol. 254:110–116. 2013. View Article : Google Scholar : PubMed/NCBI
32	Kalburgi NB, Muley A, Shivaprasad BM and Koregol AC: Expression profile of IL-35 mRNA in gingiva of chronic periodontitis and aggressive periodontitis patients: A semiquantitative RT-PCR study. Dis Markers. 35:819–823. 2013. View Article : Google Scholar : PubMed/NCBI
33	Nakajima T, Ueki-Maruyama K, Oda T, Ohsawa Y, Ito H, Seymour GJ and Yamazaki K: Regulatory T-cells infiltrate periodontal disease tissues. J Dent Res. 84:639–643. 2005. View Article : Google Scholar : PubMed/NCBI
34	Olsen I: From the Acta Prize Lecture 2014: The periodontal-systemic connection seen from a microbiological standpoint. Acta Odontol Scand. 73:563–568. 2015. View Article : Google Scholar : PubMed/NCBI
35	Linden GJ and Herzberg MC: Working group 4 of the joint EFP/AAP workshop: Periodontitis and systemic diseases: A record of discussions of working group 4 of the joint EFP/AAP workshop on periodontitis and systemic diseases. J Periodontol. 84 4 Suppl:S20–S23. 2013. View Article : Google Scholar : PubMed/NCBI
36	Paquette DW: The periodontal infection-systemic disease link: A review of the truth or myth. J Int Acad Periodontol. 4:101–109. 2002.PubMed/NCBI