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2020年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, 2020

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.2020.01.006

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30033-9#%20