清华董晨团队揭示发烧对Th17细胞分化的影响 作者： 发布时间：/2/13 16:16:02 清华大学董晨和王小虎合作的一项最新研究发现，高温可以调控制辅助性T17（Th17）细胞的分化和致病性。相关论文在线发表在2月11日的《免疫》上。
研究人员发现在体外高温选择性地调节Th17细胞分化以增强白介素17（IL-17）、IL-17F和IL-22表达。与37 C以下相比，在发热温度（38.5 C 39.5 C）下生成的Th17细胞具有强致病性基因的表达，并具有体内促炎活性。从机制上讲，发热温度促进了SMAD4转录因子的SUMO化，以促进其核定位。在体外以及改良的自身免疫性疾病模型中，SMAD4的缺失有选择地消除了发热温度对Th17细胞分化的影响。因此，该结果证明发烧在适应性免疫反应中起关键作用，并影响了自身免疫性疾病。
据了解，发烧是进化上保守的对感染的生理反应，通常也与许多自身免疫性疾病有关，但发烧在T细胞分化和自身免疫中的作用仍不清楚。辅助性T17（Th17）细胞在宿主防御和自身炎症性疾病中至关重要，具有不同的表型和致病性。
附：英文原文
Title: Febrile Temperature Critically Controls the Differentiation and Pathogenicity of T Helper 17 Cells
Author: Xiaohu Wang, Lu Ni, Siyuan Wan, Xiaohong Zhao, Xiao Ding, Anne Dejean, Chen Dong
Issue Volume: February 11,
Abstract: Fever, an evolutionarily conserved physiological response to infection, is also commonlyassociated with many autoimmune diseases, but its role in T cell differentiation andautoimmunity remains largely unclear. T helper 17 (Th17) cells are critical in hostdefense and autoinflammatory diseases, with distinct phenotypes and pathogenicity.Here, we show that febrile temperature selectively regulated Th17 cell differentiationin vitro in enhancing interleukin-17 (IL-17), IL-17F, and IL-22 expression. Th17 cells generatedunder febrile temperature (38.5 C 39.5 C), compared with those under 37 C, showedenhanced pathogenic gene expression with increased pro-inflammatory activities in vivo. Mechanistically, febrile temperature promoted SUMOylation of SMAD4 transcriptionfactor to facilitate its nuclear localization; SMAD4 deficiency selectively abrogatedthe effects of febrile temperature on Th17 cell differentiation both in vitro and ameliorated an autoimmune disease model. Our results thus demonstrate a criticalrole of fever in shaping adaptive immune responses with implications in autoimmunediseases.
DOI: 10.1016/j.immuni..01.006
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期刊信息
Immunity：《免疫》，创刊于1994年。隶属于细胞出版社，最新if：21.522
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