[1]相萍萍 刘超.滤泡辅助性T细胞、滤泡调节性T细胞与自身免疫性 甲状腺疾病[J].国际内分泌代谢杂志,2019,39(03):168-172.[doi:10.3760/cma.j.issn.1673-4157.2019.03.006]
 Xiang Pingping,Liu Chao.T foliicular helper cells, T follicular regulatory cells and autoimmune thyroid disease[J].International Journal of Endocrinology and Metabolism,2019,39(03):168-172.[doi:10.3760/cma.j.issn.1673-4157.2019.03.006]
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滤泡辅助性T细胞、滤泡调节性T细胞与自身免疫性 甲状腺疾病()
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《国际内分泌代谢杂志》[ISSN:1673-4157/CN:12-1383/R]

卷:
39
期数:
2019年03期
页码:
168-172
栏目:
综述
出版日期:
2019-05-20

文章信息/Info

Title:
T foliicular helper cells, T follicular regulatory cells and autoimmune thyroid disease
作者:
相萍萍 刘超
南京中医药大学附属中西医结合医院内分泌代谢病科; 江苏省中医药研究院 210028
Author(s):
Xiang Pingping Liu Chao
Endocrine and Diabetes Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China
关键词:
滤泡辅助性T细胞 滤泡调节性T细胞 自身免疫性甲状腺疾病 自身抗体
Keywords:
T foliicular helper cells T foliicular regulatory cells Autoimmune thyroid disease Autoantibodies
DOI:
10.3760/cma.j.issn.1673-4157.2019.03.006
摘要:
自身抗体升高是自身免疫性甲状腺疾病(AITD)的主要特点,这种变化有赖于CD4+T细胞与B细胞相互作用。滤泡辅助性T细胞(Tfh)是一类新的CD4+T细胞亚群,主要功能是促进生发中心形成,辅助B细胞分泌高亲和力抗体、促进抗体类别转换,滤泡调节性T细胞(Tfr)与Tfh有共同表征,以各种方式抑制Tfh细胞和(或)B细胞来特异性调节生发中心反应,抑制抗体产生。研究发现,AITD患者外周血Tfr/Tfh比例失衡,外周血及甲状腺组织内Tfh比例显著增加,并与甲状腺激素和甲状腺自身抗体等水平呈正相关,经治疗后Tfh比例降低。深入研究Tfh、Tfr,调节自身抗体水平可能成为AITD治疗的新方向。
Abstract:
Elevated autoantibodies, which are generated by the interaction of CD4+T cells with B cells, are main features of autoimmune thyroid disease(AITD). Follicular helper T cells(Tfh )are a new class of CD4+T cell that specialize in stimulating germinal centre(GC)formation, helping naive B cells to secrete high-affinity antibodies, to promote antibody class switching in GC. Follicular regulatory T cells(Tfr)share the same molecules with Tfh. Tfr can specifically suppress Tfh and B cells to control the GC reaction so as to restrain the production of autoantibody. Studies showed there existed imbalance of Tfh/Tfr and increased percentages of circulating Tfh, a positive correlation between the percentages of circulating Tfh and serum concentrations of thyroid hormone and thyroid autoantibodies in patients with AITD, and decreased percentage of circulating Tfh after treatment. Further study of Tfh and Tfr, especially the regulation of autoantibodies may become a new direction for the treatment of AITD.

参考文献/References:

[1] McLeod DS,Caturegli P,Cooper DS,et al.Variation in rates of autoimmune thyroid disease by race/ethnicity in US military personnel[J].JAMA,2014,311(15):1563-1565.DOI:10.1001/jama.2013.285606.
[2] Zhang Y,Fan Y,Yu X,et al.Maternal subclinical hypothyroidism impairs neurodevelopment in rat offspring by inhibiting the CREB signaling pathway[J].Mol Neurobiol,2015,52(1):432-441.DOI:10.1007/s12035-014-8855-x.
[3] Ma CS,Deenick EK,Batten M,et al.The origins, function, and regulation of T follicular helper cells[J].J Exp Med,2012,209(7):1241-1253.DOI:10.1084/jem.20120994.
[4] Zhu Y,Zou L,Liu YC.T follicular helper cells, T follicular regulatory cells and autoimmunity[J].Int Immunol,2016,28(4):173-179.DOI:10.1093/intimm/dxv079.
[5] Liu D,Xu H,Shih C,et al.T-B-cell entanglement and ICOSL-driven feed-forward regulation of germinal centre reaction[J].Nature,2015,517(7533):214-218.DOI:10.1038/nature13803.
[6] Yusuf I,Kageyama R,Monticelli L,et al.Germinal center T follicular helper cell IL-4 production is dependent on signaling lymphocytic activation molecule receptor(CD150)[J].J Immunol,2010,185(1):190-202.DOI:10.4049/jimmunol.0903505.
[7] Wing JB,Kitagawa Y,Locci M,et al.A distinct subpopulation of CD25-T-follicular regulatory cells localizes in the germinal centers[J].Proc Natl Acad Sci U S A,2017,114(31):E6400-E6409.DOI:10.1073/pnas.1705551114.
[8] Gong Y,Tong J,Wang S.Are follicular regulatory T cells involved in autoimmune diseases?[J].Front Immunol,2017,8:1790.DOI:10.3389/fimmu.2017.01790.
[9] Nance JP,Bélanger S,Johnston RJ,et al.Cutting edge: T follicular helper cell differentiation is defective in the absence of Bcl6 BTB repressor domain function[J].J Immunol,2015,194(12):5599-5603.DOI:10.4049/jimmunol.1500200.
[10] Liu X,Lu H,Chen T,et al.Genome-wide analysis identifies Bcl6-controlled regulatory networks during T follicular helper cell differentiation[J].Cell Rep,2016,14(7):1735-1747.
[11] Spolski R,Leonard WJ.IL-21 and T follicular helper cells[J].Int Immunol,2010,22(1):7-12.DOI:10.1093/intimm/dxp112.DOI:10.1093/intimm/dxp112.
[12] Choi YS,Kageyama R,Eto D,et al.ICOS receptor instructs T follicular helper cell versus effector cell differentiation via induction of the transcriptional repressor Bcl6[J].Immunity,2011,34(6):932-946.DOI:10.1016/j.immuni.2011.03.023.
[13] Morita R,Schmitt N,Bentebibel SE,et al.Human blood CXCR5(+)CD4(+)T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion[J].Immunity,2011,34(1):108-121.DOI:10.1016/j.immuni.2010.12.012.
[14] Good-Jacobson KL,Szumilas CG,Chen L,et al.PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cells[J].Nat Immunol,2010,11(6):535-542.DOI:10.1038/ni.1877.
[15] Li X,Liang Y,LeBlanc M,et al.Function of a Foxp3 cis-element in protecting regulatory T cell identity[J].Cell,2014,158(4):734-748.DOI:10.1016/j.cell.2014.07.030.
[16] Nurieva RI,Chung Y,Martinez GJ,et al.Bcl6 mediates the development of T follicular helper cells[J].Science,2009,325(5943):1001-1005.DOI:10.1126/science.1176676.
[17] Xie MM,Koh BH,Hollister K,et al.Bcl6 promotes follicular helper T-cell differentiation and PD-1 expression in a Blimp1-independent manner in mice[J].Eur J Immunol,2017,47(7):1136-1141.DOI:10.1002/eji.201747034.
[18] Nurieva RI,Chung Y,Hwang D,et al.Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages[J].Immunity,2008,29(1):138-149.DOI:10.1016/j.immuni.2008.05.009.
[19] Gharibi T,Majidi J,Kazemi T,et al.Biological effects of IL-21 on different immune cells and its role in autoimmune diseases[J].Immunobiology,2016,221(2):357-367.DOI:10.1016/j.imbio.2015.09.021.
[20] Vogelzang A,McGuire HM,Yu D,et al.A fundamental role for interleukin-21 in the generation of T follicular helper cells[J].Immunity,2008,29(1):127-137.DOI:10.1016/j.immuni.2008.06.001.
[21] Xu L,Huang Q,Wang H,et al.The kinase mTORC1 promotes the generation and suppressive function of follicular regulatory T cells[J].Immunity,2017,47(3):538-551.e5.DOI:10.1016/j.immuni.2017.08.011.
[22] Sage PT,Francisco LM,Carman CV,et al.The receptor PD-1 controls follicular regulatory T cells in the iymph nodes and blood[J].Nat Immunol,2013,14(2):152-161.DOI:10.1038/ni. 2496.
[23] Aust G,Sittig D,Becherer L,et al.The role of CXCR5 and its ligand CXCL13 in the compartmentalization of lymphocytes in thyroids affected by autoimmune thyroid diseases[J].Eur J Endocrinol,2004,150(2):225-234.
[24] Zhu C,Ma J,Liu Y,et al.Increased frequency of follicular helper T cells in patients with autoimmune thyroid disease[J].J Clin Endocrinol Metab,2012,97(3):943-950.DOI:10.1210/jc.2011-2003.
[25] Zhang J,Ren M,Zeng H,et al.Elevated follicular helper T cells and expression of IL-21 in thyroid tissues are involved in the pathogenesis of Graves' disease[J].Immunol Res,2015,62(2):163-174.DOI:10.1007/s12026-015-8647-z.
[26] Chen J,Tian J,Tang X,et al.MiR-346 regulates CD4 CXCR5 T cells in the pathogenesis of Graves' disease[J].Endocrine,2015,49(3):752-760.DOI:10.1007/s12020-015-0546-5.
[27] Zhao J,Chen Y,Zhao Q,et al.Increased circulating Tfh17 and PD-1+Tfh cells are associated with autoantibodies in Hashimoto'sthyroiditis[J].Autoimmunity,2018,51(7):352-359.DOI:10.1080/08916934.2018.1516761.
[28] Zhao J,Chen Y,Xu Z,et al.Increased circulating follicular regulatory T cells in Hashimoto's thyroiditis[J].Autoimmunity,2018,51(7):345-351.DOI:10.1080/08916934.2018.1516759.

备注/Memo

备注/Memo:
通信作者:刘超,Email: liuchao@nfmcn.com
基金项目:国家自然科学基金(81471010); 国家中医药管理局重大疑难疾病中西医临床协作试点项目(2018); 江苏省中医药领军人才(SLJ0209)
Corresponding author: Liu Chao, Email: liuchao@nfmcn.com
Fund program:National Natural Science Foundation of China(81471010); Pilot Project on Clinical Collaboration between Chinese and Western Medicine for Major Difficult Diseases(Graves Disease)of the State Administration of Traditional Chinese Medicine(2018); Leading Talents of Traditional Chinese Medicine in Jiangsu Province(SLJ0209)
更新日期/Last Update: 2019-05-20