当前位置: X-MOL 学术Proc. Natl. Acad. Sci. U.S.A. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
CD4 T cell-intrinsic role for the T helper 17 signature cytokine IL-17: Effector resistance to immune suppression.
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2020-08-11 , DOI: 10.1073/pnas.2005010117
Michael P Crawford 1 , Sushmita Sinha 1 , Pranav S Renavikar 1 , Nicholas Borcherding 1 , Nitin J Karandikar 2
Affiliation  

Untoward effector CD4+ T cell responses are kept in check by immune regulatory mechanisms mediated by CD4+ and CD8+ T cells. CD4+ T helper 17 (Th17) cells, characterized by IL-17 production, play important roles in the pathogenesis of autoimmune diseases (such as arthritis, multiple sclerosis, psoriasis, inflammatory bowel disease, among others) and in the host response to infection and cancer. Here, we demonstrate that human CD4+ T cells cells exposed to a Th17-differentiating milieu are significantly more resistant to immune suppression by CD8+ T cells compared to control Th0 cells. This resistance is mediated, in part, through the action of IL-17A, IL-17F, and IL-17AF heterodimer through their receptors (IL-17RA and IL-17RC) on CD4+ T cells themselves, but not through their action on CD8+ T cells or APC. We further show that IL-17 can directly act on non-Th17 effector CD4+ T cells to induce suppressive resistance, and this resistance can be reversed by blockade of IL-1β, IL-6, or STAT3. These studies reveal a role for IL-17 cytokines in mediating CD4-intrinsic immune resistance. The pathways induced in this process may serve as a critical target for future investigation and immunotherapeutic intervention.



中文翻译:

T 辅助细胞 17 标志性细胞因子 IL-17 的 CD4 T 细胞内在作用:对免疫抑制的效应抵抗。

不良效应 CD4+ T 细胞反应受到 CD4+ 和 CD8+ T 细胞介导的免疫调节机制的控制。CD4+ T 辅助 17 (Th17) 细胞以产生 IL-17 为特征,在自身免疫性疾病(如关节炎、多发性硬化、银屑病、炎症性肠病等)的发病机制以及宿主对感染和癌症。在这里,我们证明与对照 Th0 细胞相比,暴露于 Th17 分化环境的人类 CD4+ T 细胞对 CD8+ T 细胞的免疫抑制具有显着更强的抵抗力。这种耐药性部分是通过 IL-17A、IL-17F 和 IL-17AF 异二聚体通过它们的受体(IL-17RA 和 IL-17RC)对 CD4+ T 细胞本身的作用介导的,而不是通过它们对 CD8+ 的作用介导的T 细胞或 APC。我们进一步表明,IL-17 可以直接作用于非 Th17 效应 CD4+ T 细胞以诱导抑制性耐药,并且可以通过阻断 IL-1β、IL-6 或 STAT3 来逆转这种耐药性。这些研究揭示了 IL-17 细胞因子在介导 CD4 固有免疫抗性中的作用。在此过程中诱导的通路可作为未来研究和免疫治疗干预的关键目标。

更新日期:2020-08-11
down
wechat
bug