缺失 Aire 的树突状细胞促进 T 滤泡辅助细胞的分化。
Aire deficient dendritic cells promote the T follicular helper cells differentiation.
机构信息
Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin, 130021, China; Department of Intensive Care Unit, First Hospital, Jilin University, Changchun, Jilin, 130021, China.
Department of Rheumatology, First Hospital, Jilin University, Changchun, Jilin, 130021, China.
出版信息
Immunobiology. 2019 Jul;224(4):539-550. doi: 10.1016/j.imbio.2019.04.007. Epub 2019 Apr 19.
Autoimmune regulator (Aire), primarily expressed in medullary thymic epithelial cells (mTECs), maintains central immune tolerance through the clearance of self-reactive T cells. Aire can also be expressed in dendritic cells (DCs), and DCs can mediate T follicular helper (T) cell differentiation and self-reactive B cell activation through inducible costimulator molecule ligand (ICOSL) and interleukin 6 (IL-6), which can cause autoimmune diseases. To confirm whether Aire in DCs affects T cell differentiation and to determine the role of Aire in the maintenance of peripheral immune tolerance, this study observed the effects of Aire deficiency on T cells using Aire knockout mice. The results showed that Aire deficiency caused increased number of T cells, both in vivo and in vitro. Further studies showed that Aire deficiency promoted T differentiation through the upregulation of ICOSL and IL-6 in DCs. Thus Aire could suppress the expression of ICOSL and IL-6 to inhibit T cell differentiation.
自身免疫调节因子 (Aire) 主要在髓质胸腺上皮细胞 (mTECs) 中表达，通过清除自身反应性 T 细胞来维持中枢免疫耐受。Aire 也可以在树突状细胞 (DCs) 中表达，而 DCs 可以通过诱导共刺激分子配体 (ICOSL) 和白细胞介素 6 (IL-6) 来介导滤泡辅助性 T (Tfh) 细胞分化和自身反应性 B 细胞激活，从而导致自身免疫性疾病。为了确认 DCs 中的 Aire 是否会影响 T 细胞分化，并确定 Aire 在维持外周免疫耐受中的作用，本研究使用 Aire 敲除小鼠观察了 Aire 缺失对 T 细胞的影响。结果表明，Aire 缺失导致体内和体外 T 细胞数量增加。进一步的研究表明，Aire 缺失通过上调 DCs 中的 ICOSL 和 IL-6 促进了 T 细胞分化。因此，Aire 可以通过抑制 ICOSL 和 IL-6 的表达来抑制 T 细胞分化。
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