Extracellular matrix protein 1 promotes follicular helper T cell differentiation and antibody production

被引：40

作者：

He, Lan ^{[1
,2
]}

Gu, Wangpeng ^{[1
,3
]}

Wang, Meng ^{[4
]}

Chang, Xiaoyan ^{[4
]}

Sun, Xiaoyu ^{[4
]}

Zhang, Yuan ^{[1
]}

Lin, Xuan ^{[2
,4
]}

Yan, Chenghua ^{[1
]}

Fan, Weiguo ^{[4
]}

Su, Pan ^{[1
]}

Wang, Yanming ^{[1
,3
]}

Yi, Chunyan ^{[4
]}

Lin, Guomei ^{[1
]}

Li, Li ^{[4
]}

Jiang, Yu ^{[5
,6
]}

Lu, Junxia ^{[2
]}

Dong, Chen ^{[5
,6
]}

Wang, Haikun ^{[4
]}

Sun, Bing ^{[1
]}

机构：

[1] Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, State Key Lab Cell Biol,CAS Ctr Excellence Mol Ce, Shanghai 200031, Peoples R China

[2] ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China

[3] Univ Sci & Technol China, Sch Life Sci, Hefei 230026, Anhui, Peoples R China

[4] Chinese Acad Sci, Univ Chinese Acad Sci, Inst Pasteur Shanghai, CAS Key Lab Mol Virol & Immunol, Shanghai 200031, Peoples R China

[5] Tsinghua Univ, Inst Immunol, Beijing 100084, Peoples R China

[6] Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2018年 / 115卷 / 34期

基金：

中国国家自然科学基金;

关键词：

follicular helper T cells; antibody responses; ECM1; CD4 T cell differentiation; IL-2-pSTAT5; signaling; CXC CHEMOKINE RECEPTOR-5; ICOS; BCL6; INDUCTION; RESPONSES; STAT5; PD-1;

D O I：

10.1073/pnas.1801196115

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

T-follicular helper (T-FH) cells are a subset of CD4(+) helper T cells that help germinal center (GC) B-cell differentiation and high-affinity antibody production during germinal center reactions. Whether important extracellular molecules control T-FH differentiation is not fully understood. Here, we demonstrate that a secreted protein extracellular matrix protein 1 (ECM1) is critical for T-FH differentiation and antibody response. A lack of ECM1 inhibited T-FH cell development and impaired GC B-cell reactions and antigen-specific antibody production in an antigen-immunized mouse model. ECM1 was induced by IL-6 and IL-21 in T-FH cells, promoting T-FH differentiation by down-regulating the level of STAT5 phosphorylation and up-regulating Bcl6 expression. Furthermore, injection of recombinant ECM1 protein into mice infected with PR8 influenza virus promoted protective immune responses effectively, by enhancing T-FH differentiation and neutralizing antibody production. Collectively, our data identify ECM1 as a soluble protein to promote T-FH cell differentiation and antibody production.

引用

页码：8621 / 8626

页数：6

共 26 条

[1] The role of ICOS in the CXCR5+ follicular B helper T cell maintenance in vivo [J].