Department of Microbiology and Immunology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN.
Department of Cancer Immunology, Genentech, South San Francisco, CA.
J Exp Med. 2019 Jun 3;216(6):1450-1464. doi: 10.1084/jem.20182376. Epub 2019 May 3.
CD4 T helper 17 (Th17) cells protect vertebrate hosts from extracellular pathogens at mucosal surfaces. Th17 cells form from naive precursors when signals from the T cell antigen receptor (TCR) and certain cytokine receptors induce the expression of the RORγt transcription factor, which activates a set of Th17-specific genes. Using T cell-specific loss-of-function experiments, we find that two components of the Polycomb repressive complex 1.1 (PRC1.1), BCL6 corepressor (BCOR) and KDM2B, which helps target the complex to unmethylated CpG DNA islands, are required for optimal Th17 cell formation in mice after infection. Genome-wide expression and BCOR chromatin immunoprecipitation studies revealed that BCOR directly represses , , and , whose products inhibit Th17 differentiation. Together, the results suggest that the PRC1.1 components BCOR and KDM2B work together to enhance Th17 cell formation by repressing Th17 fate suppressors.
CD4+T 辅助 17（Th17）细胞在黏膜表面保护脊椎动物宿主免受细胞外病原体的侵害。当 T 细胞抗原受体（TCR）和某些细胞因子受体的信号诱导 RORγt 转录因子的表达时，Th17 细胞从幼稚前体中形成，该转录因子激活一组 Th17 特异性基因。使用 T 细胞特异性功能丧失实验，我们发现多梳抑制复合物 1.1（PRC1.1）的两个成分，BCL6 核心抑制因子（BCOR）和 KDM2B，有助于将复合物靶向未甲基化的 CpG DNA 岛，这是感染后小鼠中最佳 Th17 细胞形成所必需的。全基因组表达和 BCOR 染色质免疫沉淀研究表明，BCOR 直接抑制，，和，其产物抑制 Th17 分化。总之，结果表明 PRC1.1 成分 BCOR 和 KDM2B 通过抑制 Th17 命运抑制物共同增强 Th17 细胞的形成。
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