DataSheet_1_JunB Is Critical for Survival of T Helper Cells.pdf

Clonal expansion and differentiation of various T helper subsets, such as Th1, Th2, and Th17 cells, depend on a complex of transcription factors, IRF4 and a BATF-containing AP-1 heterodimer. A major BATF heterodimeric partner, JunB, regulates Th17 differentiation, but the role of JunB in other T helper subsets is not well understood. Here we demonstrate that JunB is required for clonal expansion of Th1, Th2 and Th17 cells. In mice immunized with lipopolysaccharide (LPS), papain, or complete Freund’s adjuvant (CFA), which induce predominantly Th1, Th2 and Th17 cells, respectively, accumulation of antigen-primed, Junb-deficient CD4+ T cells is significantly impaired. TCR-stimulated Junb-deficient CD4+ T cells are more sensitive to apoptosis, although they showed largely normal proliferation and cellular metabolism. JunB directly inhibits expression of genes involved in apoptosis, including Bcl2l11 (encoding Bim), by promoting IRF4 DNA binding at the gene locus. Taken together, JunB serves a critical function in clonal expansion of diverse T helper cells by inhibiting their apoptosis.

克隆扩增与分化是多种T辅助细胞亚群，如Th1、Th2和Th17细胞，所依赖的转录因子复合体，包括IRF4与含有BATF的AP-1异源二聚体。BATF的主要异源二聚体伴侣JunB调节Th17细胞的分化，但JunB在其他T辅助细胞亚群中的作用尚不明确。本研究表明，JunB对于Th1、Th2和Th17细胞的克隆扩增是必需的。在用脂多糖（LPS）、木瓜蛋白酶或完全弗氏佐剂（CFA）免疫的实验小鼠中，分别诱导出以Th1、Th2和Th17细胞为主的免疫反应，这些佐剂分别能够诱导出Th1、Th2和Th17细胞。在这些小鼠中，抗原预处理的Junb缺陷型CD4+ T细胞的积累显著受损。与TCR刺激的正常CD4+ T细胞相比，Junb缺陷型CD4+ T细胞对凋亡更为敏感，尽管它们的增殖和细胞代谢功能基本正常。JunB通过促进IRF4与基因座上的DNA结合，直接抑制参与凋亡的基因表达，包括编码Bim的Bcl2l11。综上所述，JunB通过抑制T辅助细胞的凋亡，在多种T辅助细胞的克隆扩增中发挥着至关重要的作用。