FOXP3型
生物
效应器
细胞生物学
免疫学
白细胞介素2受体
细胞分化
癌症研究
转录组
免疫系统
T细胞
基因表达
基因
遗传学
作者
Eui Ho Kim,David J. Gasper,Song Hee Lee,Erin H. Plisch,John Svaren,M. Suresh
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2013-12-24
卷期号:192 (3): 985-995
被引量:96
标识
DOI:10.4049/jimmunol.1302378
摘要
Abstract Variants of the Bach2 gene are linked to vitiligo, celiac disease, and type 1 diabetes, but the underlying immunological mechanisms are unknown. In this study, we demonstrate that Bach2 plays crucial roles in maintaining T cell quiescence and governing the differentiation, activation, and survival of Foxp3+ regulatory T (Treg) cells. Bach2-deficient T cells display spontaneous activation and produce elevated levels of Th1/Th2-type cytokines. Without Bach2, Treg cells exhibit diminished Foxp3 expression, depleted numbers, hyperactivation, enhanced proliferation, and profound loss of competitive fitness in vivo. Mechanistically, reduced survival of Bach2-deficient Treg cells was associated with reduced Bcl-2 and Mcl-1 levels and elevated Bim/Bcl-2 ratio. Additionally, Bach2 deficiency induced selective loss of Helios−Foxp3+ Treg cells and a Treg cell transcriptome skewed toward the Th1/Th2 effector program at the expense of the Treg program. In vitro experiments confirmed that Bach2: 1) is indispensable for TCR/TGF-β–induced Foxp3 expression; and 2) mitigates aberrant differentiation of Treg cells by repression of the competing Gata3-driven Th2 effector program. Importantly, perturbations in the differentiation of induced Treg cells was linked to a fatal Th2-type chronic inflammatory lung disease in Bach2-deficient mice. Thus, Bach2 enforces T cell quiescence, promotes the development and survival of Treg lineage, restrains aberrant differentiation of Treg cells, and protects against immune-mediated diseases.
科研通智能强力驱动
Strongly Powered by AbleSci AI