Estrogen regulates T helper 17 phenotype and localization in experimental autoimmune arthritis.
Estrogen regulates T helper 17 phenotype and localization in experimental autoimmune arthritis.
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雌激素调节T助手17表型和实验性自身免疫性关节炎的定位。
DOI：
10.1186/s13075-015-0548-y
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发表时间：
2015-02-13
影响因子：
4.9
通讯作者：
Islander U
中科院分区：
文献类型：
--
作者：
Andersson A;Stubelius A;Karlsson MN;Engdahl C;Erlandsson M;Grahnemo L;Lagerquist MK;Islander U
许多自身免疫性疾病的发生和进展具有性别偏见，这可能是由内分泌激素的免疫调节特性解释的。雌二醇治疗有效抑制实验性自身免疫性关节炎。产生白细胞介素-17的辅助性T细胞（Th 17）是几种自身免疫性疾病，特别是类风湿性关节炎中的关键参与者。本研究旨在探讨雌激素对实验性关节炎中Th 17细胞的影响。用17β-雌二醇（E2）或安慰剂治疗的卵巢切除DBA/1小鼠进行胶原诱导的关节炎（CIA），并评估关节炎的发展。用流式细胞仪检测关节和淋巴结中的Th 17细胞。还在卵巢切除雌激素受体α-敲除小鼠（ERα-/-）和野生型同窝仔中检查了淋巴结Th 17细胞，这些小鼠用E2或安慰剂治疗并经历抗原诱导的关节炎。与对照组相比，E2治疗的CIA小鼠关节炎的严重程度降低，关节中的Th 17细胞减少。有趣的是，E2治疗的小鼠在疾病的早期阶段淋巴结中显示出增加的Th 17细胞，依赖于ERα。E2增加淋巴结Th 17细胞上C-C趋化因子受体6（CCR 6）的表达以及淋巴结内相应C-C趋化因子配体20（CCL 20）的表达。这是第一项研究，其中E2对Th 17细胞的影响已在实验性自身免疫性关节炎的特点。我们报告说，E2治疗的结果在淋巴结中的Th 17细胞的增加，在关节炎发展的早期阶段，但导致关节中的Th 17细胞减少，在建立关节炎。我们的数据表明，这可能是由干扰CCR 6-CCL 20途径引起的，这对Th 17细胞迁移很重要。这项研究有助于了解雌激素在自身免疫性关节炎的发展中的作用，并为自身免疫性疾病的性别偏见研究开辟了新的领域。本文的在线版本（doi：10.1186/s13075-015-0548-y）包含补充材料，可供授权用户使用。
The incidence and progression of many autoimmune diseases are sex-biased, which might be explained by the immunomodulating properties of endocrine hormones. Treatment with estradiol potently inhibits experimental autoimmune arthritis. Interleukin-17-producing T helper cells (Th17) are key players in several autoimmune diseases, particularly in rheumatoid arthritis. The aim of this study was to investigate the effects of estrogen on Th17 cells in experimental arthritis. Ovariectomized DBA/1 mice treated with 17β-estradiol (E2) or placebo were subjected to collagen-induced arthritis (CIA), and arthritis development was assessed. Th17 cells in joints and lymph nodes were studied by flow cytometry. Lymph node Th17 cells were also examined in ovariectomized estrogen receptor α–knockout mice (ERα−/−) and wild-type littermates, treated with E2 or placebo and subjected to antigen-induced arthritis. E2-treated mice with established CIA showed reduced severity of arthritis and fewer Th17 cells in joints compared with controls. Interestingly, E2-treated mice displayed increased Th17 cells in lymph nodes during the early phase of the disease, dependent on ERα. E2 increased the expression of C-C chemokine receptor 6 (CCR6) on lymph node Th17 cells as well as the expression of the corresponding C-C chemokine ligand 20 (CCL20) within lymph nodes. This is the first study in which the effects of E2 on Th17 cells have been characterized in experimental autoimmune arthritis. We report that E2 treatment results in an increase of Th17 cells in lymph nodes during the early phase of arthritis development, but leads to a decrease of Th17 in joints during established arthritis. Our data suggest that this may be caused by interference with the CCR6-CCL20 pathway, which is important for Th17 cell migration. This study contributes to the understanding of the role of estrogen in the development of autoimmune arthritis and opens up new fields for research concerning the sex bias in autoimmune disease. The online version of this article (doi:10.1186/s13075-015-0548-y) contains supplementary material, which is available to authorized users.
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影响因子：
4.9
作者：
Jochems C;Islander U;Erlandsson M;Verdrengh M;Ohlsson C;Carlsten H
通讯作者：
Carlsten H
影响因子：
4
作者：
DeSelm, Carl J.;Takahata, Yoshifumi;Warren, Julia;Chappel, Jean C.;Khan, Taimur;Li, Xiaoxia;Liu, Caini;Choi, Yongwon;Kim, Youngmi Faith;Zou, Wei;Teitelbaum, Steven L.
通讯作者：
Teitelbaum, Steven L.
影响因子：
5.5
作者：
Lengi, Andrea J.;Phillips, Rebecca A.;Ahmed, S. Ansar
通讯作者：
Ahmed, S. Ansar
影响因子：
27.4
作者：
d'Elia, HF;Larsen, A;Carlsten, H
通讯作者：
Carlsten, H
影响因子：
4.9
作者：
Engdahl C;Börjesson AE;Forsman HF;Andersson A;Stubelius A;Krust A;Chambon P;Islander U;Ohlsson C;Carlsten H;Lagerquist MK
通讯作者：
Lagerquist MK