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

Sungjun Park, Seungwon Lee, Choong Gu Lee, Guk Yeol Park, Hyebeen Hong, Jeon Soo Lee, Young Min Kim, Sung Bae Lee, Daehee Hwang, Youn Soo Choi, John D. Fryer, Sin Hyeog Im, Seung Woo Lee, Yoontae Lee

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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

Original languageEnglish (US)
Article number16037
JournalNature communications
Volume8
DOIs
StatePublished - Jul 12 2017

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Park, S., Lee, S., Lee, C. G., Park, G. Y., Hong, H., Lee, J. S., Kim, Y. M., Lee, S. B., Hwang, D., Choi, Y. S., Fryer, J. D., Im, S. H., Lee, S. W., & Lee, Y. (2017). Capicua deficiency induces autoimmunity and promotes follicular helper T cell differentiation via derepression of ETV5. Nature communications, 8, [16037]. https://doi.org/10.1038/ncomms16037