A retinoic acid-dependent checkpoint in the development of CD4+ T cell-mediated immunity

被引:100
|
作者
Pino-Lagos, Karina [1 ]
Guo, Yanxia [1 ]
Brown, Chrysothemis [3 ]
Alexander, Matthew P. [1 ]
Elgueta, Raul [3 ]
Bennett, Kathryn A. [1 ]
De Vries, Victor [1 ]
Nowak, Elizabeth [1 ]
Blomhoff, Rune [4 ]
Sockanathan, Shanthini [5 ]
Chandraratna, Roshantha A. [6 ]
Dmitrovsky, Ethan [2 ]
Noelle, Randolph J. [1 ,3 ]
机构
[1] Norris Cotton Canc Ctr, Dartmouth Med Sch, Dept Microbiol & Immunol, Lebanon, NH 03756 USA
[2] Dartmouth Med Sch, Dept Pharmacol & Toxicol, Hanover, NH 03755 USA
[3] Kings Coll London, Guys Hosp, MRC, Ctr Transplantat, London SE1 9RT, England
[4] Univ Oslo, Inst Basic Med Sci, Dept Nutr, N-0372 Oslo, Norway
[5] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA
[6] IO Therapeut, Santa Ana, CA 92705 USA
来源
JOURNAL OF EXPERIMENTAL MEDICINE | 2011年 / 208卷 / 09期
基金
美国国家卫生研究院; 英国医学研究理事会;
关键词
DENDRITIC CELLS; VITAMIN-A; SMALL-INTESTINE; RECEPTOR-ALPHA; EXPRESSION; DIFFERENTIATION; GENERATION; INDUCTION; SYSTEM;
D O I
10.1084/jem.20102358
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
It is known that vitamin A and its metabolite, retinoic acid (RA), are essential for host defense. However, the mechanisms for how RA controls inflammation are incompletely understood. The findings presented in this study show that RA signaling occurs concurrent with the development of inflammation. In models of vaccination and allogeneic graft rejection, whole body imaging reveals that RA signaling is temporally and spatially restricted to the site of inflammation. Conditional ablation of RA signaling in T cells significantly interferes with CD4(+) T cell effector function, migration, and polarity. These findings provide a new perspective of the role of RA as a mediator directly controlling CD4(+) T cell differentiation and immunity.
引用
收藏
页码:1767 / 1775
页数:9
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