Retinoic Acid Is Essential for Th1 Cell Lineage Stability and Prevents Transition to a Th17 Cell Program

被引：119

作者：

Brown, Chrysothemis C. ^{[1
]}

Esterhazy, Daria ^{[2
]}

Sarde, Aurelien ^{[1
]}

London, Mariya ^{[2
]}

Pullabhatla, Venu ^{[3
,4
]}

Osma-Garcia, Ines ^{[1
]}

al-Bader, Raya ^{[1
]}

Ortiz, Carla ^{[1
]}

Elgueta, Raul ^{[1
]}

Arno, Matthew ^{[5
]}

de Rinaldis, Emanuele ^{[3
,4
,6
]}

Mucida, Daniel ^{[2
]}

Lord, Graham M. ^{[1
,3
,4
]}

Noelle, Randolph J. ^{[1
,7
]}

机构：

[1] Kings Coll London, Div Transplantat Immunol & Mucosal Biol, London SE1 9RT, England

[2] Rockefeller Univ, Lab Mucosal Immunol, New York, NY 10065 USA

[3] Guys & St Thomas Natl Hlth Serv Fdn Trust, Biomed Res Ctr, Natl Inst Hlth Res, London SE1 9RT, England

[4] Kings Coll London, London SE1 9RT, England

[5] Kings Coll London, Genom Ctr, London SE1 9NH, England

[6] Guys Hosp, Kings Coll London, Sch Med, Div Canc Studies, London SE1 9RT, England

[7] Dartmouth Med Sch, Dept Microbiol & Immunol, Lebanon, NH 03756 USA

来源：

IMMUNITY | 2015年 / 42卷 / 03期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

TRANSCRIPTIONAL ACTIVATION; INTERFERON-GAMMA; TGF-BETA; T-BET; DIFFERENTIATION; T(H)17; PLASTICITY; CHROMATIN; INCREASES; DISEASE;

D O I：

10.1016/j.immuni.2015.02.003

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

CD4(+) T cells differentiate into phenotypically distinct T helper cells upon antigenic stimulation. Regulation of plasticity between these CD4+ T-cell lineages is critical for immune homeostasis and prevention of autoimmune disease. However, the factors that regulate lineage stability are largely unknown. Here we investigate a role for retinoic acid (RA) in the regulation of lineage stability using T helper 1 (Th1) cells, traditionally considered the most phenotypically stable Th subset. We found that RA, through its receptor RAR alpha, sustains stable expression of Th1 lineage specifying genes, as well as repressing genes that instruct Th17-cell fate. RA signaling is essential for limiting Th1-cell conversion into Th17 effectors and for preventing pathogenic Th17 responses in vivo. Our study identifies RA-RAR alpha as a key component of the regulatory network governing maintenance and plasticity of Th1-cell fate and defines an additional pathway for the development of Th17 cells.

引用

页码：499 / 511

页数：13

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