Tet调控Th17/Treg细胞分化参与自身免疫性疾病发病的研究进展

doi:10.3760/cma.j.issn.1007-1245.2022.11.005

国际医药卫生导报 ›› 2022, Vol. 28 ›› Issue (11): 1500-1504.DOI: 10.3760/cma.j.issn.1007-1245.2022.11.005

Tet调控Th17/Treg细胞分化参与自身免疫性疾病发病的研究进展

姜冠桐¹ 周瑾² 薛海波¹

¹滨州医学院附属医院内分泌科，滨州　256603； ²烟台毓璜顶医院内分泌科，烟台　264000

收稿日期:2022-01-17 出版日期:2022-06-01 发布日期:2022-06-15
通讯作者: 薛海波，Email：xuehaibo@sina.com
基金资助:
山东省研究生教育创新计划项目（20038612）；

滨州医学院附属医院科研创新团队（202031）；

滨州医学院附属医院后备领军人才（JC2019-03）

Tet in regulation of Th17/Treg cell differentiation and in participatesion of pathogenesis of autoimmune diseases

Jiang Guantong¹, Zhou Jin², Xue Haibo¹

¹Department of Endocrinology, Binzhou Medical University Hospital, Binzhou 256603, China;
²Department of Endocrinology, Yantai Yuhuangding Hospital, Yantai 264000, China

Received:2022-01-17 Online:2022-06-01 Published:2022-06-15
Contact: Xue Haibo, Email: xuehaibo@sina.com
Supported by:
Innovation Program of Post-graduate Education in Shandong Province (20038612);

Scientific Research and Innovation Team Project of Binzhou Medical University Hospital (202031);

Project for Reserved Leading Talents of Binzhou Medical University Hospital (JC2019-03)

摘要/Abstract

摘要： CD4⁺T细胞是人体免疫重要的一部分，其中辅助性T细胞17（T helper cell 17，Th17）和调节性T细胞（regulatory T cells，Treg）两个新近发现的CD4⁺T细胞亚群在自身免疫疾病的发生发展中也起关键作用。Th17细胞能够引起自身免疫和炎性反应，而Treg细胞抑制疾病发生并维持免疫稳态；10～11易位蛋白（ten-eleven translocation，Tet）作为DNA去甲基化的关键因子，当其缺失时能够影响Th17/Treg免疫平衡。本文针对Tet调控Th17/Treg细胞分化参与自身免疫疾病发生发展的研究进展作一综述。

关键词: Tet, Th17, Treg, Th17/Treg, 自身免疫性疾病

Abstract: CD4⁺ T cells are an important part of human immunity. T helper cell 17 (Th17) and regulatory T cells (Treg), two newly discovered subsets of CD4⁺ T cells, play a key role in the occurrence and development of autoimmune diseases. Th17 cause autoimmunity and inflammation, while Treg inhibit the emergence of diseases and maintain immune homeostasis. Ten-eleven translocation (Tet), as a key factor in DNA demethylation, affects the Th17/Treg balance and involves in the progression of autoimmune diseases when it is absent. This review focuses on the research of the regulatory role of Tet on Th17/Treg cell immunization balance and the possible pathogenesis of autoimmune diseases.

Key words: Tet, Th17, Treg, Th17/Treg, Autoimmune diseases

姜冠桐, 周瑾, 薛海波. Tet调控Th17/Treg细胞分化参与自身免疫性疾病发病的研究进展[J]. 国际医药卫生导报, 2022, 28(11): 1500-1504.

Jiang Guantong, Zhou Jin, Xue Haibo. Tet in regulation of Th17/Treg cell differentiation and in participatesion of pathogenesis of autoimmune diseases[J]. International Medicine and Health Guidance News, 2022, 28(11): 1500-1504.

参考文献

[1] Zhu J, Yamane H, Paul WE. Differentiation of effector CD4 T cell populations[J]. Annual Review of Immunology, 2010, 28(1):445-489.DOI: 10.1146/annurev- immunol- 030409-101212.

[2] Yang XO, Pappu BP, Nurieva R, et al. T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma[J]. Immunity, 2008,28(1):29-39. DOI: 10.1016/j.immuni.2007.11.016.

[3] Zhou L, Lopes JE, Chong MM, et al. TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function[J]. Nature, 2008,453(7192):236-240. DOI: 10.1038/nature06878.

[4] Long D, Chen Y, Wu H, et al. Clinical significance and immunobiology of IL-21 in autoimmunity[J]. J Autoimmun, 2019,99:1-14. DOI: 10.1016/j.jaut.2019. 01.013.

[5] Niu W, Xu Y, Zha X, et al. IL-21/IL-21R signaling aggravated respiratory inflammation induced by intracellular bacteria through regulation of CD4⁺ T cell subset responses[J]. J Immunol, 2021,206(7):1586-1596. DOI: 10.4049/jimmunol.2001107.

[6] Yu N, Li X, Song W, et al. CD4(+)CD25 (+)CD127 (low/-) T cells: a more specific Treg population in human peripheral blood[J]. Inflammation, 2012,35(6):1773-1780. DOI: 10.1007/s10753-012-9496-8.

[7] Shevach EM, Thornton AM. tTregs, pTregs, and iTregs: similarities and differences[J]. Immunol Rev, 2014,259(1):88-102. DOI: 10.1111/imr.12160.

[8] Kimura A, Kishimoto T. IL-6: regulator of Treg/Th17 balance[J]. Eur J Immunol, 2010,40(7):1830-1835. DOI: 10.1002/eji.201040391.

[9] Takeuchi Y, Hirota K, Sakaguchi S. Impaired T cell receptor signaling and development of T cell-mediated autoimmune arthritis[J]. Immunol Rev, 2020,294(1):164-176. DOI: 10.1111/imr.12841.

[10] Cluxton D, Petrasca A, Moran B, et al. Differential regulation of human Treg and Th17 cells by fatty acid synthesis and glycolysis[J]. Front Immunol, 2019,10:115. DOI: 10.3389/fimmu.2019.00115.

[11] Westfall S, Caracci F, Zhao D, et al. Microbiota metabolites modulate the T helper 17 to regulatory T cell (Th17/Treg) imbalance promoting resilience to stress-induced anxiety- and depressive-like behaviors[J]. Brain Behav Immun, 2021,91:350-368. DOI: 10.1016/j.bbi.2020. 10.013.

[12] Paradowska-Gorycka A, Wajda A, Romanowska- Próchnicka K, et al. Th17/Treg-related transcriptional factor expression and cytokine profile in patients with rheumatoid arthritis[J]. Front Immunol, 2020,11:572858. DOI: 10.3389/fimmu.2020.572858.

[13] Yan JB, Luo MM, Chen ZY, et al. The function and role of the Th17/Treg cell balance in inflammatory bowel disease[J]. J Immunol Res, 2020,2020:8813558. DOI: 10.1155/2020/8813558.

[14] Yuliasih Y, Rahmawati LD, Putri RM. Th17/Treg ratio and disease activity in systemic lupus erythematosus[J]. Caspian J Intern Med, 2019,10(1):65-72. DOI: 10.22088/cjim.10.1.65.

[15] 吕蒙,沈洁,李章芳,等.Treg/Th17细胞及相关细胞因子在Graves眼病中的作用及机制[J].南方医科大学学报,2014,34(12):1809-1813.DOI:10.3969/j.issn.1673-4254. 2014.12.21.

[16] Rodríguez-Muñoz A, Martínez-Hernández R, Ramos-Leví AM, et al. Circulating microvesicles regulate Treg and Th17 differentiation in human autoimmune thyroid disorders[J]. J Clin Endocrinol Metab, 2015,100(12):E1531-1539. DOI: 10.1210/jc.2015-3146.

[17] Li C, Yuan J, Zhu YF, et al. Imbalance of Th17/Treg in different subtypes of autoimmune thyroid diseases[J]. Cell Physiol Biochem, 2016,40(1-2):245-252. DOI: 10.1159/000452541.

[18] Li D, Guo B, Wu H, et al. TET family of dioxygenases: crucial roles and underlying mechanisms[J]. Cytogenet Genome Res, 2015,146(3):171-180. DOI: 10.1159/000438853.

[19] Tian YP, Zhu YM, Sun XH, et al. Multiple functions of ten-eleven translocation 1 during tumorigenesis[J]. Chin Med J (Engl), 2016,129(14):1744-1751. DOI: 10.4103/0366-6999.185873.

[20] Sun F, Abreu-Rodriguez I, Ye S, et al. TET1 is an important transcriptional activator of TNFα expression in macrophages[J]. PLoS One, 2019,14(6):e0218551. DOI: 10.1371/journal.pone.0218551.

[21] Kunimoto H, Nakajima H. TET2: a cornerstone in normal and malignant hematopoiesis[J]. Cancer Sci, 2021,112(1):31-40. DOI: 10.1111/cas.14688.

[22] Cong B, Zhang Q, Cao X. The function and regulation of TET2 in innate immunity and inflammation[J]. Protein Cell, 2021,12(3):165-173. DOI: 10.1007/s13238-020- 00796-6.

[23] Montagner S, Leoni C, Emming S, et al. TET2 regulates mast cell differentiation and proliferation through catalytic and non-catalytic activities[J]. Cell Rep, 2016,15(7):1566-1579. DOI: 10.1016/j.celrep.2016.04.044.

[24] Lio CW, Zhang J, González-Avalos E, et al. Tet2 and Tet3 cooperate with B-lineage transcription factors to regulate DNA modification and chromatin accessibility[J]. Elife, 2016,5:e18290. DOI: 10.7554/eLife.18290.

[25] Ichiyama K, Chen T, Wang X, et al. The methylcytosine dioxygenase Tet2 promotes DNA demethylation and activation of cytokine gene expression in T cells[J]. Immunity, 2015,42(4):613-626. DOI: 10.1016/j.immuni. 2015.03.005.

[26] Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3[J]. Science, 2003,299(5609):1057-1061. DOI: 10.1126/science.1079490.

[27] Korn T, Muschaweckh A. Stability and maintenance of Foxp3+ treg cells in non-lymphoid microenvironments[J]. Front Immunol, 2019,10:2634. DOI: 10.3389/fimmu. 2019. 02634.

[28] Deng G, Song X, Fujimoto S, et al. Foxp3 post-translational modifications and treg suppressive activity[J]. Front Immunol, 2019,10:2486. DOI: 10.3389/fimmu.2019. 02486.

[29] Zheng Y, Josefowicz S, Chaudhry A, et al. Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate[J]. Nature, 2010,463(7282):808-812. DOI: 10.1038/nature08750.

[30] Ohkura N, Hamaguchi M, Morikawa H, et al. T cell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and complementary events required for Treg cell development[J]. Immunity, 2012,37(5):785-799. DOI: 10.1016/j.immuni.2012. 09.010.

[31] Nakatsukasa H, Oda M, Yin J, et al. Loss of TET proteins in regulatory T cells promotes abnormal proliferation, Foxp3 destabilization and IL-17 expression[J]. Int Immunol, 2019,31(5):335-347. DOI: 10.1093/intimm/dxz008.

[32] Yue X, Lio CJ, Samaniego-Castruita D, et al. Loss of TET2 and TET3 in regulatory T cells unleashes effector function[J]. Nat Commun, 2019,10(1):2011. DOI: 10.1038/s41467-019-09541-y.

[33] Yang R, Qu C, Zhou Y, et al. Hydrogen sulfide promotes Tet1- and tet2-mediated Foxp3 demethylation to drive regulatory T cell differentiation and maintain immune homeostasis[J]. Immunity, 2015,43(2):251-263. DOI: 10.1016/j.immuni.2015.07.017.

[34] Someya K, Nakatsukasa H, Ito M, et al. Improvement of Foxp3 stability through CNS2 demethylation by TET enzyme induction and activation[J]. Int Immunol, 2017,29(8):365-375. DOI: 10.1093/intimm/dxx049.

[35] Yue X, Trifari S, Äijö T, et al. Control of Foxp3 stability through modulation of TET activity[J]. J Exp Med, 2016,213(3):377-397. DOI: 10.1084/jem.20151438.

[36] Sasidharan Nair V, Song MH, Oh KI. Vitamin C facilitates demethylation of the Foxp3 enhancer in a Tet-dependent manner[J]. J Immunol, 2016,196(5):2119-2131. DOI: 10.4049/jimmunol.1502352.

Tet调控Th17/Treg细胞分化参与自身免疫性疾病发病的研究进展

Tet in regulation of Th17/Treg cell differentiation and in participatesion of pathogenesis of autoimmune diseases

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