Capicua deficiency induces autoimmunity and promotes follicular helper T cell differentiation via derepression of ETV5

Nat Commun. 2017 Jul 12:8:16037. doi: 10.1038/ncomms16037.

Abstract

High-affinity antibody production through the germinal centre (GC) response is a pivotal process in adaptive immunity. Abnormal development of follicular helper T (TFH) 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 TFH cells and GC responses in a T-cell-intrinsic manner. ETV5 expression is derepressed in Cic null TFH cells and knockdown of Etv5 suppresses the enhanced TFH cell differentiation in Cic-deficient CD4+ T cells, suggesting that Etv5 is a critical CIC target gene in TFH 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 TFH cell development and autoimmunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmunity*
  • Cell Differentiation
  • DNA-Binding Proteins / metabolism*
  • Female
  • Germinal Center / physiology*
  • Homeostasis
  • Immune Tolerance
  • Male
  • Mice, Inbred C57BL
  • Repressor Proteins / physiology*
  • T-Lymphocytes, Helper-Inducer / physiology*
  • Transcription Factors / metabolism*

Substances

  • Cic protein, mouse
  • DNA-Binding Proteins
  • Etv5 protein, mouse
  • Repressor Proteins
  • Transcription Factors