Regulation of type 17 helper T-cell function by nitric oxide during inflammation
Regulation of type 17 helper T-cell function by nitric oxide during inflammation
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DOI：
10.1073/pnas.1100667108
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发表时间：
2011-05-31
影响因子：
11.1
通讯作者：
Liew, Foo Y.
中科院分区：
文献类型：
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作者：
Niedbala, Wanda;Alves-Filho, Jose C.;Liew, Foo Y.
17 型辅助 T (Th17) 细胞与许多人类自身免疫性疾病的发病机制有关。 Th17 的发育可以通过芳烃受体 (AHR) 的激活来增强，该受体的配体包括环境污染物二恶英，可能将环境因素与自身免疫性疾病患病率的增加联系起来。我们在此报告，一氧化氮 (NO) 可以抑制极化的小鼠和人类 Th17 细胞的增殖和功能。 NO 还抑制 Th17 细胞中的 AHR 表达以及 AHR 激活的下游事件，包括 IL-22、IL-23 受体和 Cyp1a1。相反，NO 不影响 AHR 缺陷小鼠的 Th17 细胞的极化。此外，缺乏诱导型一氧化氮合酶（Nos2(-/-)）的小鼠比WT小鼠发生更严重的实验性自身免疫性脑脊髓炎，AHR表达升高，IL-17A和IL-22合成增加。因此，NO 可能是一种重要的内源性调节因子，可防止 Th17 细胞过度增殖并控制环境污染物引起的自身免疫性疾病。
Type 17 helper T (Th17) cells are implicated in the pathogenesis many of human autoimmune diseases. Development of Th17 can be enhanced by the activation of aryl hydrocarbon receptor (AHR) whose ligands include the environmental pollutant dioxin, potentially linking environmental factors to the increased prevalence of autoimmune disease. We report here that nitric oxide (NO) can suppress the proliferation and function of polarized murine and human Th17 cells. NO also inhibits AHR expression in Th17 cells and the downstream events of AHR activation, including IL-22, IL-23 receptor, and Cyp1a1. Conversely, NO did not affect the polarization of Th17 cells from mice deficient in AHR. Furthermore, mice lacking inducible nitric oxide synthase (Nos2(-/-)) developed more severe experimental autoimmune encephalomyelitis than WT mice, with elevated AHR expression, increased IL-17A, and IL-22 synthesis. NO may therefore represent an important endogenous regulator to prevent overexpansion of Th17 cells and control of autoimmune diseases caused by environmental pollutants.