Research Progress on Regulatory T Cells and Their Relationship with Autoimmune Diseases
Regulatory T cells (Tregs) are a subset of T cells with immunosuppressive functions. They secrete IL-10, TGF-âand other suppressive cytokines and direct contact among cells to suppress the autoimmunity response of effector T cells, promote immune tolerance, which has a very important role in maintaining the body’s homeostasis. Foxp3 is a specific transcription factor of Treg cells and plays a key role in the regulation of Treg cell development and function. Treg and Th17 cells are derived from the differentiation of the same type of initial CD4+T cells. The direction of differentiation depends on the type of cytokines in the environment. The functions of them are opposite to each other and transform each other under certain conditions. It plays an important role in inducing immune tolerance and preventing the occurrence of autoimmune diseases (AID). Once immune imbalance, it will lead to the occurrence of immune-related diseases. The decrease of its number or function will affect the immune state of the body, cause disorders of autoimmune tolerance and lead to the occurrence of AID. This article reviews the research of Treg and their cytokines in AID in order to understand the role of Treg in the pathogenesis of AID, and open a new way for the treatment of AID.
Research Progress on Regulatory T Cells and Their Relationship with Autoimmune Diseases, Science Journal of Public Health.
Vol. 8, No. 3,
2020, pp. 83-91.
Pan HF, Leng RX, Wu GC, et al. Advance in epidemiologic studies on major autoimmune diseases. Chin J Dis Control Prev 2018, vol. 22, pp. 1093-1095, 1105.
Liu HP, Cao AT, Feng T, et al. TGF-β converts Th1 cells into Th17 cells through stimulation of Runx1 expression [J]. Eur J Immunol. 2015, vol. 45, pp. 1010-1018.
Zhivaki D, Lemoine S, Lim A, et al. Respiratory Syncytial Virus Infects Regulatory B Cells in Human Neonates via Chemokine Receptor CX3CR1 and Promotes Lung Disease Severity [J]. Immunity. 2017, vol. 46, pp. 301-314.
Sawant DV, Hamilton K, Vignali DA. Interleukin-35: Expanding Its Job Profile [J]. J Interferon Cytokine Res. 2015, vol. 35, pp. 499-512.
Castellani ML, Anogeianaki A, Felaco P, IL-35, an anti-inflammatory cytokine which expands CD4+CD25+ Treg Cells [J]. J Biol Regul Homeost Agents. 2010, vol. 24, pp. 131-135.
Bantug G, Galluzzi L, Kroemer G, et al. The spectrum of T cell metabolism in health and disease [J]. Nat Rev Immunol, 2018, vol. 18, pp. 19-34.
Noack M, Miossec P. Th17 and regulatory T cell balance in autoimmune and inflammatory diseases [J]. Autoimmun Rev, 2014, vol. 13, pp. 668-677.
Zhang L, Wang YX, Yang T, et al. A current review ofthe relationship between IL-12 and autoimmune diseases. Chin J Dis Control Prev, 2014, vol. 18, pp. 1099-1103
Nie H, Zheng Y, Li R, et al. Phosphorylation of FOXP3 controls regulatory T cell function and is inhibited by TNF-α in rheumatoid arthritis [J]. Nat Med, 2013, vol. 19, pp. 322-328.
Moradi B, Schnatzer P, Hagmann S, et al. CD4+CD25+/highCD127low/- regulatory T cells are enriched in rheuma-toid arthritis and osteoarthritis joints--analysis of frequency and phenotype in synovial membrane, synovial fluid and peripheral blood [J]. Arthritis Res Ther. 2014, vol. 16, pp. R97.
Walter GJ, Fleskens V, Frederiksen KS, et al. Phenotypic, Functional, and Gene Expression Profiling of Peripheral CD45RA+and CD45RO+CD4+CD25+CD127 (low) Treg Cells in Patients With Chronic Rheumatoid Arthritis [J]. Arthritis Rheumatol, 2016, vol. 68, pp. 103-116.
Wang W, Shao S, Jiao Z, et al. The Th17/Treg imbalance and cytokine environment in peripheral blood of patients with rheumatoid arthritis [J]. Rheumatol Int, 2012, vol. 32, pp. 887-893.
Liu YX, Zhu YF, Liu Y, et al. Quantity of Th17 and Treg cells in the peripheral blood from patients with rheumatoid arthritis: a meta analysis. J Zhengzhou Univ (Med Scie). 2015, vol. 50, pp. 606-610.
Dong L, Wang X, Tan J, et al. Decreased expression of microRNA-21 correlates with the imbalance of Th17 and Treg cells in patients with rheumatoid arthritis [J]. J Cell Mol Med. 2014, vol. 18, pp. 2213-2224.
Jain M, Attur M, Furer V, et al. Increased plasma IL-17F levels in rheumatoid arthritis patients are responsiveto methotrexate, anti-TNF, and T cell costimulatory modulation [J]. Inflammation. 2015, vol. 38, pp. 180-186.
Rosenzwajg M, Lorenzon R, Cacoub P, et al. Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial [J]. Ann Rheum Dis. 2019, vol. 78, pp. 209-217.
Astry B, Venkatesha SH, Moudgil KD. Involvement of the IL-23/IL-17 axis and the Th17/Treg balance in the patho-genesis and control of autoimmune arthritis [J]. Cytokine. 2015, vol. 74, pp. 54-61.
Lin H, Zhang GD, Tang HH, et al. The Change of CD4+CD25+ Regulatory T Cells in Patients with Rheumatoid Arthritis. J Sichuan Univ (Med Sci Edi). 2014, vol. 45, pp. 618-622.
Li ZW, Tian YF Lu PP, et al. Detection and significance of lymphocyte and tregth17 balance in patients with Rheum-atoid Arthritis. Int J Lab Med. 2019, vol. 74, pp. 2026-2028.
Xiang HY, Pan F, Yan JZ, et al. Upregulation of miR-498 suppresses Th17 cell differentiation by targeting STAT3 in rheumatoid arthritis patients. Acta Physiologica Sinica, 2018, vol. 70, pp. 167-174.
Liénart S, Merceron R, Vanderaa C, et al. Structural basis of latent TGF-β1presentation and activation by GARP on human regulatory T cells [J]. Science. 2018, vol. 362, pp. 952-956.
Bai L, Wu Y, Li HB, et al. The effects of GARP activated Tregs cells on rheumatoid arthritis and its mechanism J Practical Med, 2019, vol. 35, pp. 2276-2280.
Von Spee-Mayer C, Siegert E, Abdirama D, et al. Low-dose interleukin-2 selectively corrects regulatory T cell defects in patients with systemic lupus erythematosus [J]. Ann Rheum Dis. 2016, vol. 75, pp. 1407-1415.
Jia HY, Cheng GH. Expressions and Significance of Th17 Treg Cell and Related Cytokines in Peripheral Blood in Patients with SLE. Hebei Med, 2018, vol. 24, pp. 1277-1280.
Huang KK, Zhou CY, Yan ZT, et al. Application of AG490 to Regulation Th17/Treg Balance in Systemic Lupus Erythematosus by Blocking STAT3. Med Innovation China, 2019, vol. 16, pp. 141-145
Hu W, Wang S, Wang X, et al. Expression of Th1 /Th2 /Th17 /Treg in peripheral blood of patients with SLE and its clinical significance. Southeast Univ ( Med Sci Edi). 2019, vol. 38, pp. 308-312.
Hao HQ, Zhang SR, Li XF, et al. Value of determining Th17 and regulatory T cells in the peripheral blood in evaluating patients with systemic lupus erythematosus. Chin J Prac Inter Med, 2018, vol. 38, pp. 242-244.
Li J, Ueno A, Fort Gasia M, et al. Profiles of la mina propria T helper cell subsets discri minate between ulcerative colitis and crohn' s disease [J]. Inflamm Bowel Dis, 2016, vol. 22, pp. 1779-1792.
Iboshi Y, Nakamura K, Ihara E, et al. Multigene analysis unveils distinctive expression profiles of helper T-cell related genes in the intestinal mucosa that discri minate between ulcerative colitis and crohn's disease [J]. InflammBowel Dis, 2014, vol. 20, pp. 967-977.
Chao K, Zhang S, Yao J, et al. Imbalances of CD4 (+) T-cell subgroups in Crohn’s disease and their relationship with disease activity and prognosis [J]. J Gastroenterol Hepatol, 2014, vol. 29, pp. 1808-1814.
D’Ambrosio A, Cossu A, Amendola A, et al. Lamina propria CD4+LAP+regulatory T cells are increased in active ulcerative colitis but show increased IL-17 expression and reduced suppressor activity [J]. J Crohns Colitis, 2016, vol. 10, pp. 346-353.
Xu Z, Wei C, Zhang RU, et al. Epigallocatechin-3-gallate-induced inhibition of interleukin-6 release and adjustment of the regulatory T/T helper 17 cell balance in the treatment of colitis in mice [J]. Exp Ther Med. 2015, vol. 10, pp. 2231-2238.
Wang CYL, Sun JG, Geng Y, et al. Progress of Treg/Thl7 immune axis imbalance in ulcerative colitis and its detection by them ethod of flow cytometry. J Immuno. 2015, vol. 31, pp. 541-544.
Lee SY, Lee SH, Yang EJ, et al. Metformin ameliorates inflammatory bowel disease by suppression of the STAT3 signaling pathway and regulation of the between Th17/Treg balance. PLoS One, 2015, vol. 10, pp. e135858.
Zhao XJ, Ma JJ, Zhu YJ, et al. Alterations of Th17/Treg cells in peripheral blood and serum inflammatory biomarkers in patients with Crohn’s disease and its clinical significance. J Nanjing MedUniv (Nat Scie) 2017, vol. 37, pp. 1000-1004.
Alper A, Zhang L, Pashankar DS. Correlation of erythrocyte sedimentation rate andC-reactive protein with pediatric.
inflammatory bowel disease activity. J Pediatr Gastroenterol Nutr, 2017, vol. 65, pp. e25-27.
Wang Y, Wu LP, Fu J, et al. Hyperthyroid monkeys:a nonhuman primate model of experimental Graves’disease. J Endocrinol, 2013, vol. 219, pp. 183-193.
Bao QY, Xu YS, Yang HY. Regulatory T Cells and Endocrine Diseases. Medical Recapitulate. 2014, vol. 20, pp. 3278-3280.
Glick AB, Wodzinski A, Fu P, et al. Impairment of regulatory T cell function in autoimmune thyroid disease. Thyroid, 2013, vol. 23, pp. 871-878.
Klatka M, Grywalska E, Partyka M, et al. Th17 and Treg cells in adolescents with Graves’disease, Impact of treatment with methimazole on these cell subsets. Autoimmunity, 2014, vol. 47, pp. 201-211.
Li ZY, Li CX, Cui LR, et al. Transformation analysis of peripheral blood CD4+ CD25+ Treg, Foxp3 mRNA level and biochemical index of elderly patients with Graves before and after treatment with Iodine-131 and methimazole. Chinese J Control Endemic Diseases, 2018, vol. 33, pp. 617-621.
Biglar Chopoghlou S, Hanifi N, Varjoshani NJ. A comparative study of uncertainty and coping strategies of patients with multiple sclerosis for members and nonmembers in peer groups. Health Care Women Int. 2019, vol. 1, pp. 1-14.
Ravyn D, Goodwin B, Lowney R, et al. Continuous learning in multiple sclerosis care: a qualitative study of the expanded learning model for systems. Int J Med Educ. 2019, vol. 10, pp. 122-128.
Lamers I, Raats J, Spaas J, et al. Intensity-dependent clinical effects of an individualized technology-supported task-oriented upper limb training program in Multiple Sclerosis: A pilot randomized controlled trial. Mult Scler Relat Disord. 2019, vol. 34, pp. 119-127.
Kleinewietfeld M, Hafler DA. Regulatory T cells in autoimmune neuroin flammation. Immunol Rev. 2014, vol. 259, pp. 231-244.
Li D. Detection of Tlymphocyte subsets and related cytokines in 31 cases of multiple sclerosis. J Tianjin Medi University. 2019, vol. 25, pp. 80-83.
Jiang JA, Liu CP, Xue Q, et al. Changes and clinical significance of peripheral CD28-T cell subsets in patients with multiplesclerosis. Chin J Neuroimmunol & Neurol, 2019, vol. 26, pp. 391-396.
Zhu JD, Wang ZQ, Zhang PN. The Imbalance of Immunity Between Th17 and CD4+CD25+Regulatory T Cell in Patients with Sjgren's Syndrome. J Radio Immuno, 2012, vol. 25, pp. 301-303.
Alunno A, Petrillo MG, Nocentini G, et al. Characterization of a new regulatory CD+4 T cell subset in primary Sjgren' s syndrome. Rheumatology (Oxford), 2013, vol. 52, pp. 1387-1396.
Wang QK, Yuan X, Zhou YB, et al. Effect of costimulatory molecules B7-H4 on T lymphocyte subsets of NOD mice in Sjgren's syndrome. Chin J Dis Control Prev. 2018, vol. 22, pp. 731-735.
Li H, Wang L, Pang Y, et al. In patients with chronic aplastic anemia, bone marrowderived MSCs regulate the Treg/Th17 balance by influencing the Notch/RBP-J/FOXP3/RORγt pathway. Sci Rep. 2017, vol. 7, pp. 42488.
Wang K, Wan L, Liu J. Relationship between changes of lung function and Notch pathway and regula-tory T cells in pSS rats. Chin J Immu, 2019, vol. 35, pp. 2191-2194.
Raychaudhuri SK, Saxena A, Raychaudhuri SP. Role of IL-17 in the pathogenesis of psoriatic arthritis and axial spondyloarthritis. Clin Rheumatol. 2015, vol. 34, pp. 1019-1023.
Zhang L, Li Y, Yang X, et al. Characterization of Th17 and FoxP3 (+) Treg Cells in Paediatric Psoriasis Patients. Scand J Immunol. 2016, vol. 83, pp. 174-180.
Keijsers RR, Joosten I, Hendriks AG, et al. Balance of Treg versus T-effector cells during systemic treatment with adalimumab and topicaltreatment with calcipotriol-betamethasone dipropionate ointment. Exp Dermatol. 2015, vol. 24, pp. 65-67.