Regulatory immune cells: a review of the novel paradigm of primary Sjogren's syndrome

Year 2023, Volume: 6 Issue: 1, 215 - 219, 12.01.2023

Selda Ucar

https://doi.org/10.32322/jhsm.1188641

Abstract

Primary Sjögren's Syndrome (pSS) is an autoimmune disease that mostly affects women. Patients with pSS experience dry mouth and eyes in addition to signs of systemic disease. pSS was considered a Th1 autoimmune disease for many years. However, in various studies, it has been shown that dysregulation of regulatory cells play critical role in the pathogenesis of the disease. This review focuses on studies supporting this view and answers questions about the role of regulatory cells in the pathogenesis of pSS.

Keywords

Arthritis, rheumatoid, regulatory T-cells, regulatory B-cells, primary Sjogren, follicular regulatory T-cells

References

• Du W, Han M, Zhu X, et al. The multiple roles of b cells in the pathogenesis of Sjögren's syndrome. Front Immunol 2021; 12: 684999.
• Nocturne G, Mariette X. Advances in understanding the pathogenesis of primary Sjögren's syndrome. Nat Rev Rheumatol 2013; 9: 544–56.
• Srivastava A., Makarenkova HP. Innate immunity and biological therapies for the treatment of Sjögren's syndrome. Int J Mol Sci 2020; 21: 9172.
• Uptodate, https://www.uptodate.com/contents/overview-of-the-management-and-prognosis-of-sjogrens- syndrome?search=sjogren%20treat. Baer NA, Vivino FB. 30 July 2021.
• Negrini S, Emmi G, Greco M, et al. Sjögren's syndrome: a systemic autoimmune disease. Clin Exp Med 2022; 22: 9–25.
• Rosser EC, Mauri C. Regulatory B cells: origin, phenotype, and function. Immunity 2015; 42: 607–12.
• Belcheva KT, Chaudhuri J. Maintenance of lineage identity: lessons from a B cell. J Immun 2022; 209: 2073-81.
• Furuzawa-Carballeda J, Hernández-Molina G, Lima G, Rivera-Vicencio Y, Férez-Blando K, Llorente L. Peripheral regulatory cells immunophenotyping in primary Sjögren's syndrome: a cross-sectional study. Arthritis Res Ther 2013; 15: R68.
• Mielle J, Nutz A, Guillpain P, et al. IL-10-producing regulatory B cells are present and functional in primary Sjögren patients. Immunol Res 2021; 69: 107–13.
• Lin X, Wang X, Xiao F, et al. IL-10- producing regulatory B cells restrain the T follicular helper cell response in primary Sjögren’s syndrome. Cell Mol Immunol 2019, 16: 921–31.
• Bowman SJ, Fox R, Dörner T, et al. Safety and efficacy of subcutaneous inalumab (VAY736) in patients with primary Sjögren's syndrome: a randomised, double-blind, placebo-controlled, phase 2b dose-finding trial. Lancet 2022; 399: 161-71.
• Matsushita T. Regulatory and effector B cells: Friends or foes? J Dermatol Sci 2019; 93: 2–7.
• Alunno A, Carubbi F, Bistoni O. T Regulatory and T Helper 17 Cells in primary Sjögren's syndrome: facts and perspectives. Mediators Inflamm 2015; 243723.
• Shevach EM, Thornton AM. tTregs, pTregs, and iTregs: similarities and differences. Immunol Rev 2014; 259: 88–102.
• Josefowicz SZ, Rudensky A. Control of regulatory T cell lineage commitment and maintenance. Immunity 2009; 30: 616–25.
• Hsieh CS, Lee HM, Lio CW. Selection of regulatory T cells in the thymus. Nat Rev Immunol 2012; 12: 157–67.
• Chen W, Jin W, Hardegen N, et al. Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 2003; 198: 1875–86.
• Yadav M, Stephan S, Bluestone JA. Peripherally induced tregs - role in immune homeostasis and autoimmunity. Front Immunol 2013; 4: 232.
• Yadav M, Louvet C, Davini D, et al. Neuropilin-1 distinguishes natural and inducible regulatory T cells among regulatory T cell subsets in vivo. J Exp Med 2012; 209: 1713: 1–19.
• Newton R, Priyadharshini B, Turka LA. Immunometabolism of regulatory T cells. Nat Immunol 2016; 17: 618–25.
• Zeng H, Yang K, Cloer C, et al. Chi H.mTORC1 couples immune signals and metabolic programming to establish T(reg)-cell function. Nature 2013; 499: 485–90.
• Zeng H, Chi H. Metabolic control of regulatory T cell development and function. Trends Immunol 2015; 36: 3–12.
• Li X, Li X, Qian L, et al. T regulatory cells are markedly diminished in diseased salivary glands of patients with primary Sjögren's syndrome. J Rheumatol 2007; 34: 2438-45.
• Li XM, Li XP, Qian L, et al.Expression of CD4+ CD25+ regulatory T cells in peripheral blood and salivary gland of patients with primary Sjögren's syndrome. Zhonghua Yi Xue Za Zhi 2007; 87: 1034-6.
• Banica L, Besliu A, Pistol G, et al. Quantification and molecular characterization of regulatory T cells in connective tissue diseases. Autoimmunity 2009; 42: 41–9.
• Gottenberg JE, Lavie F, Abbed K, et al. CD4 CD25high regulatory T cells are not impaired in patients with primary Sjögren's syndrome. J Autoimmun 2005; 24: 235-42.
• Sarigul M, Yazisiz V, Bassorgun CI, et al. The numbers of Foxp3 + Treg cells are positively correlated with higher grade of infiltration at the salivary glands in primary Sjogren's syndrome. Lupus 2010; 19: 138–45.
• Christodoulou MI, Kapsogeorgou EK, Moutsopoulos NM, Moutsopoulos HM. Foxp3+ T-regulatory cells in Sjogren's syndrome: correlation with the grade of the autoimmune lesion and certain adverse prognostic factors. Am J Pathol 2008; 173: 1389–96.
• Furuzawa-Carballeda J, Hernández-Molina G, Lima G, Rivera-Vicencio Y, Férez-Blando K, Llorente, L. Peripheral regulatory cells immunophenotyping in primary Sjögren's syndrome: a cross-sectional study. Arthritis Res Ther 2013; 15: R68.
• Alunna A, Petrillo MG, Nocentini G, et al. Characterization of a new regulatory CD4+ T cell subset in primary Sjogren's syndrome. Rheumatology (Oxford) 2013; 52: 1387–96.
• Li L, He J, Zhu L, et al. The clinical relevance of IL-17producing CD4+CD161+ cell and its subpopulations in primary Sjögren’s syndrome. J Immunol Res 2015: 307453.
• Sage PT, Sharpe AH. The multifaceted functions of follicular regulatory T cells. Curr Opin Immunol 2020; 67: 68–74.
• Linterman MA, Pierson W, Lee SK, et al. Foxp3+ follicular regulatory T cells control the germinal center response. Nat Med 2011; 17: 975–82.
• Chung Y, Tanaka S, Chu F, et al. Follicular regulatory T cells expressing Foxp 3 and Bcl-6 suppress germinal center reactions. Nat Med 2011; 17: 983-88.
• Wing JB, Tekgüç M, Sakaguchi S. Control of Germinal Center Responses by T-Follicular Regulatory Cells. Front Immunol 2018; 9: 1910.
• Wollenberg I, Agua-Doce A, Hernández A, et al. Regulation of the germinal center reaction by Foxp3+ follicular regulatory T cells. J Immunol 2011; 187: 4553–60.
• Vanderleyden I, Fra-Bido SC, Innocentin S, et al. Follicular Regulatory T Cells Can Access the Germinal Center Independently of CXCR5. Cell Rep 2020; 30: 611-9.
• Fonseca VR, Ribeiro F, Graca L. T follicular regulatory (Tfr) cells: dissecting the complexity of Tfr-cell compartments. Immunol Rev 2019; 288: 112–27.
• Fonseca VR, Agua-Doce A, Maceiras AR, et al. Human blood Tfr cells are indicators of ongoing humoral activity not fully licensed with suppressive function. Sci Immunol 2017; 2: eaan1487.
• Fonseca VR, Romão VC, Agua-Doce A, et al. The ratio of blood T follicular regulatory cells to T follicular helper cells marks ectopic lymphoid structure formation while activated follicular helper T cells indicate disease activity in primary Sjögren's syndrome. Arth. Rheumatol 2018; 70: 774–84.
• Verstappen GM, Nakshbandi U, Mossel E, et al. Is the T follicular regulatory: follicular helper T cell ratio in blood a biomarker for ectopic lymphoid structure formation in Sjogren's syndrome? Arthritis Rheumatol 2018; 70: 1354-5.
• Kim JW, Lee J, Hong SM, et al. Park SH. Circulating CCR7(lo)PD-1(hi) follicular helper T cells indicate disease activity and glandular inflammation in patients with primary Sjogren’s syndrome. Immun Netw 2019; 19-26.