TIGIT A2Ar 依赖性抗葡萄膜炎调节性 T 细胞是与自身免疫性葡萄膜炎消退相关的调节性 T 细胞的一个新亚群。
TIGIT A2Ar-Dependent anti-uveitic Treg cells are a novel subset of Tregs associated with resolution of autoimmune uveitis.
机构信息
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Department of Ophthalmology/Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
出版信息
J Autoimmun. 2020 Jul;111:102441. doi: 10.1016/j.jaut.2020.102441. Epub 2020 Mar 20.
Regulatory T cells (Tregs) are necessary to prevent autoimmune disease. As such, stable FoxP3 expression is required for the proper function of Tregs in the control of autoimmune disease. Different Treg subsets that utilize different mechanisms of suppression have been identified. The T-cell immunoglobulin immunoreceptor tyrosine-based inhibitory motif (TIGIT) is a relatively new Treg cell marker that has a suppressive function. We have previously identified the adenosine 2A receptor (A2Ar) as a requirement for the emergence of Tregs following resolution of autoimmune disease. Using a FoxP3-GFP-Cre reporter mouse, we identify FoxP3 and 'exFoxP3' cells, show FoxP3 and not exFoxP3 cells are suppressive. We further show FoxP3 cells express TIGIT, and are induced through A2Ar in healthy volunteers, but not patients with autoimmune disease. Furthermore, we show Tregs emerge in the target tissue at the onset of autoimmune disease in an A2Ar-dependent manner. In summary, we identify a novel subset of TIGIT Tregs that are induced through stimulation of the A2Ar.
调节性 T 细胞（Tregs）对于预防自身免疫性疾病是必需的。因此，Tregs 在控制自身免疫性疾病中发挥适当功能需要稳定的 FoxP3 表达。已经鉴定出利用不同抑制机制的不同 Treg 亚群。T 细胞免疫球蛋白免疫受体酪氨酸基抑制基序（TIGIT）是一种相对较新的 Treg 细胞标志物，具有抑制功能。我们之前已经确定腺苷 2A 受体（A2Ar）是自身免疫性疾病缓解后 Tregs 出现的必需条件。使用 FoxP3-GFP-Cre 报告小鼠，我们鉴定出 FoxP3 和“exFoxP3”细胞，表明 FoxP3 而不是 exFoxP3 细胞具有抑制作用。我们进一步表明 FoxP3 细胞表达 TIGIT，并通过 A2Ar 在健康志愿者中诱导，但在自身免疫性疾病患者中没有诱导。此外，我们表明 Tregs 以 A2Ar 依赖性方式在自身免疫性疾病发作时出现在靶组织中。总之，我们鉴定出一种新型的通过刺激 A2Ar 诱导的 TIGIT Tregs 亚群。
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