Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 73673, Republic of Korea.
Division of Integrative Bioscience and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk 73673, Republic of Korea.
Nat Commun. 2017 Jul 12;8:16037. doi: 10.1038/ncomms16037.
High-affinity antibody production through the germinal centre (GC) response is a pivotal process in adaptive immunity. Abnormal development of follicular helper T (T) cells can induce the GC response to self-antigens, subsequently leading to autoimmunity. Here we show the transcriptional repressor Capicua/CIC maintains peripheral immune tolerance by suppressing aberrant activation of adaptive immunity. CIC deficiency induces excessive development of T cells and GC responses in a T-cell-intrinsic manner. ETV5 expression is derepressed in Cic null T cells and knockdown of Etv5 suppresses the enhanced T cell differentiation in Cic-deficient CD4 T cells, suggesting that Etv5 is a critical CIC target gene in T cell differentiation. Furthermore, we identify Maf as a downstream target of the CIC-ETV5 axis in this process. These data demonstrate that CIC maintains T-cell homeostasis and negatively regulates T cell development and autoimmunity.
高亲和力抗体通过生发中心（GC）反应产生，是适应性免疫的关键过程。滤泡辅助 T（T）细胞的异常发育会诱导 GC 对自身抗原产生反应，从而导致自身免疫。在这里，我们表明转录抑制因子 Capicua/CIC 通过抑制适应性免疫的异常激活来维持外周免疫耐受。CIC 缺陷以 T 细胞内在的方式诱导 T 细胞的过度发育和 GC 反应。在 Cic 缺失的 T 细胞中，ETV5 的表达被去抑制，而 Etv5 的敲低抑制了 Cic 缺陷型 CD4 T 细胞中增强的 T 细胞分化，表明 Etv5 是 T 细胞分化中 CIC 的关键靶基因。此外，我们确定 Maf 是该过程中 CIC-ETV5 轴的下游靶标。这些数据表明 CIC 维持 T 细胞的动态平衡，并负调控 T 细胞的发育和自身免疫。
