FOXP3+ regulatory T cells in autoimmune hepatitis are fully functional and not reduced in frequency
FOXP3+ regulatory T cells in autoimmune hepatitis are fully functional and not reduced in frequency
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DOI：
10.1016/j.jhep.2012.02.029
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发表时间：
2012-07-01
影响因子：
25.7
通讯作者：
Herkel, Johannes
中科院分区：
文献类型：
--
作者：
Peiseler, Moritz;Sebode, Marcial;Herkel, Johannes
背景和目标：自身免疫性肝炎（AIH）的发病机制尚不清楚，但有人认为AIH可能与CD4+CD25+FOXP3+调节性T细胞（Treg）的数量或功能损伤有关，Treg是对自身抗原免疫耐受的重要介质。然而，Treg在AIH中的作用尚不清楚，因为早期报道Treg损伤的研究仅使用CD25作为标志物，其不能明确区分Treg和活化的效应T细胞。方法：我们使用可以区分Treg和活化的效应T细胞的当前染色方案评估Treg的频率和抑制功能。与健康受试者相比，AIH患者血液中CD4+CD25（高）CD127（低）FOXP3+ Treg细胞的频率没有降低，如流式细胞术所示，并通过定量FOXP3基因的Treg特异性去甲基化证实。此外，从AIH患者中分离的Treg的抑制功能与从健康受试者中分离的Treg的抑制功能相似，表明Treg功能在AIH患者中未受损。然而，我们观察到患有活动性疾病的AIH患者的Treg频率明显高于处于缓解状态的患者，这表明Treg频率可能随着炎症程度的增加而增加。事实上，肝脏组织学中FOXP 3 + Treg的分析显示，AIH患者的肝内Treg频率高于NASH患者，并且与肝脏的炎症活动相关。结论：AIH患者循环Treg细胞的频率和功能并未受损。(C)2012年欧洲肝脏研究协会。Elsevier B.V.出版，保留所有权利。
Background & Aims: The pathogenesis of autoimmune hepatitis (AIH) is not understood, but it was suggested that AIH may be related to a numerical or functional impairment of CD4+CD25+FOXP3+ regulatory T cells (Treg), which are important mediators of immune tolerance to self-antigens. However, the role of Treg in AIH is not clear, since earlier studies reporting Treg impairment had used only CD25 as marker that cannot unambiguously distinguish Treg from activated effector T cells.Methods: We assessed the frequency and suppressor function of Treg using current staining protocols that can distinguish Treg from activated effector T cells.Results: The frequency of CD4+CD25(high)CD127(low) FOXP3+ Treg cells in blood of AIH patients was not reduced compared to healthy subjects, as shown by flow cytometry and confirmed by quantifying Treg-specific demethylation of the FOXP3 gene. Moreover, the suppressor function of Treg isolated from AIH patients was similar to that of Treg isolated from healthy subjects, indicating that Treg function was not impaired in AIH patients. However, we observed that the Treg frequency was significantly higher in those AIH patients with active disease than in those who were in a state of remission, suggesting that the Treg frequency may increase with the degree of inflammation. Indeed, analysis of FOXP3+ Treg in liver histology revealed that the intra-hepatic Treg frequency was higher in AIH patients than in NASH patients and correlated with the inflammatory activity of the liver.Conclusions: The frequency and function of circulating Treg cells is not impaired in AIH. (C) 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.