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

9 Citations (Scopus)

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

Fingerprint

T-cells
Helper-Inducer T-Lymphocytes
Autoimmunity
Germinal Center
Cell Differentiation
Adaptive Immunity
cells
T-Lymphocytes
Autoantigens
immunity
Peripheral Tolerance
Immune Tolerance
Genes
Chemical activation
Antibody Formation
homeostasis
Homeostasis
Antibodies
antigens
antibodies

ASJC Scopus subject areas

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

Cite this

Capicua deficiency induces autoimmunity and promotes follicular helper T cell differentiation via derepression of ETV5. / Park, Sungjun; Lee, Seungwon; Lee, Choong Gu; Park, Guk Yeol; Hong, Hyebeen; Lee, Jeon Soo; Kim, Young Min; Lee, Sung Bae; Hwang, Daehee; Choi, Youn Soo; Fryer, John D.; Im, Sin Hyeog; Lee, Seung Woo; Lee, Yoontae.

In: Nature Communications, Vol. 8, 16037, 12.07.2017.

Research output: Contribution to journalArticle

Park, S, Lee, S, Lee, CG, Park, GY, Hong, H, Lee, JS, Kim, YM, Lee, SB, Hwang, D, Choi, YS, Fryer, JD, Im, SH, Lee, SW & Lee, Y 2017, 'Capicua deficiency induces autoimmunity and promotes follicular helper T cell differentiation via derepression of ETV5', Nature Communications, vol. 8, 16037. https://doi.org/10.1038/ncomms16037
Park, Sungjun ; Lee, Seungwon ; Lee, Choong Gu ; Park, Guk Yeol ; Hong, Hyebeen ; Lee, Jeon Soo ; Kim, Young Min ; Lee, Sung Bae ; Hwang, Daehee ; Choi, Youn Soo ; Fryer, John D. ; Im, Sin Hyeog ; Lee, Seung Woo ; Lee, Yoontae. / Capicua deficiency induces autoimmunity and promotes follicular helper T cell differentiation via derepression of ETV5. In: Nature Communications. 2017 ; Vol. 8.
@article{813cfe2d3ed54ec495dc0e2d978e822e,
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",
year = "2017",
month = "7",
day = "12",
doi = "10.1038/ncomms16037",
language = "English (US)",
volume = "8",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Capicua deficiency induces autoimmunity and promotes follicular helper T cell differentiation via derepression of ETV5

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.

UR - http://www.scopus.com/inward/record.url?scp=85024124192&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85024124192&partnerID=8YFLogxK

U2 - 10.1038/ncomms16037

DO - 10.1038/ncomms16037

M3 - Article

C2 - 28855737

AN - SCOPUS:85024124192

VL - 8

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 16037

ER -