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

doi:10.1038/ncomms16037

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

Department of Brain Sciences

Research output: Contribution to journal › Article › peer-review

34 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 language	English
Article number	16037
Journal	Nature Communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms16037
State	Published - 12 Jul 2017

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title = "Capicua deficiency induces autoimmunity and promotes follicular helper T cell differentiation via derepression of ETV5",

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.",

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

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AU - Park, Sungjun

AU - Lee, Seungwon

AU - Lee, Choong Gu

AU - Park, Guk Yeol

AU - Hong, Hyebeen

AU - Lee, Jeon Soo

AU - Kim, Young Min

AU - Lee, Sung Bae

AU - Hwang, Daehee

AU - Choi, Youn Soo

AU - Fryer, John D.

AU - Im, Sin Hyeog

AU - Lee, Seung Woo

AU - Lee, Yoontae

PY - 2017/7/12

Y1 - 2017/7/12

N2 - 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.

AB - 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.

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VL - 8

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

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