Essential Role for Retinoic Acid in the Promotion of CD4+ T Cell Effector Responses via Retinoic Acid Receptor Alpha

被引：314

作者：

Hall, Jason A. ^{[1
,5
]}

Cannons, Jennifer L. ^{[2
]}

Grainger, John R. ^{[1
]}

Dos Santos, Liliane M. ^{[1
]}

Hand, Timothy W. ^{[1
]}

Naik, Shruti ^{[1
,5
]}

Wohlfert, Elizabeth A. ^{[1
]}

Chou, David B. ^{[1
]}

Oldenhove, Guillaume ^{[1
]}

Robinson, Melody ^{[3
]}

Grigg, Michael E. ^{[4
]}

Kastenmayer, Robin ^{[3
]}

Schwartzberg, Pamela L. ^{[2
]}

Belkaid, Yasmine ^{[1
]}

机构：

[1] NIAID, Mucosal Immun Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA

[2] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA

[3] NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA

[4] NIAID, Mol Parasitol Unit, NIH, Bethesda, MD 20892 USA

[5] Univ Penn, Immunol Grad Grp, Philadelphia, PA 19104 USA

来源：

IMMUNITY | 2011年 / 34卷 / 03期

基金：

美国国家卫生研究院;

关键词：

VITAMIN-A-DEFICIENCY; DENDRITIC CELLS; TOXOPLASMA-GONDII; SIGNALING PATHWAY; SMALL-INTESTINE; TH17; CELLS; FOXP3; DIFFERENTIATION; MICE; METABOLISM;

D O I：

10.1016/j.immuni.2011.03.003

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Vitamin A and its metabolite, retinoic acid (RA) are implicated in the regulation of immune homeostasis via the peripheral induction of regulatory T cells. Here we showed RA was also required to elicit proinflammatory CD4(+) helper T cell responses to infection and mucosal vaccination. Retinoic acid receptor alpha (RAR alpha) was the critical mediator of these effects. Antagonism of RAR signaling and deficiency in RAR alpha (Rara(-/-)) resulted in a cell-autonomous CD4(+) T cell activation defect, which impaired intermediate signaling events, including calcium mobilization. Altogether, these findings reveal a fundamental role for the RA-RAR alpha axis in the development of both regulatory and inflammatory arms of adaptive immunity and establish nutritional status as a broad regulator of adaptive T cell responses.

引用

页码：435 / 447

页数：13

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