在IL-33驱动的气道炎症中,TRAF4对于ST2+记忆和Th2细胞扩张至关重要
Jianxin Xiao1, Xing Chen1, Weiwei Liu1
1Inflammation and Immunity, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA.
JCI insight
|August 22, 2023
概括
瘤亡因子受体相关因子4 (TRAF4) 在2型呼吸道炎症中对T细胞增殖至关重要. 缺少TRAF4会影响IL-33诱导的ST2+mTh2细胞生长,并减少肺炎.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 瘤亡因子受体相关因子4 (TRAF4) 调节2型免疫反应.
- 在T助手2 (Th2) 细胞中TRAF4的精确机制尚未完全理解.
- 介素-33 (IL-33) 驱动2型气道炎症.
研究的目的:
- 为了研究TRAF4在ST2+记忆Th2 (mTh2) 细胞中在IL-33介导的2型气道炎症期间的作用.
- 阐明TRAF4影响Th2细胞反应的细胞和分子机制.
主要方法:
- 产生T细胞特异性TRAF4缺陷 (CD4-cre Traf4fl/fl) 的小鼠.
- 在体外偏振和Th2细胞的刺激.
- 评估细胞增殖,信号通路 (AKT/mTOR,ERK1/2) 和对IL-33.3的反应中的基因表达.
- 在小鼠模型中评估肺炎和乙氨基透.
主要成果:
- 缺乏TRAF4的ST2+mTh2细胞在体外显示IL-33诱导的增殖减少.
- CD4-cre Traf4fl/fl小鼠表现出降低的ST2+mTh2细胞增殖和肺异osinophilia.
- 对于IL-33诱导的AKT/mTOR和ERK1/2通路的激活,TRAF4是必不可少的.
- 在对IL-33的反应中,TRAF4调节了Myc,Slc2a1,Slc7a1和Slc7a5的表达.
结论:
- 在ST2+mTh2细胞的增殖和功能中,TRAF4起着至关重要的作用.
- 对于IL-33介导的2型肺炎来说,TRAF4信号传递至关重要.
- 针对TRAF4可能为2型呼吸道疾病提供新的治疗策略.
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