All-trans retinoic acid mediates enhanced T reg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation

Micah J. Benson, Karina Pino-Lagos, Mario Rosemblatt, Randolph J. Noelle

Research output: Contribution to journalArticlepeer-review

627 Scopus citations

Abstract

We demonstrate that all-trans retinoic acid (RA) induces FoxP3+ adaptive T regulatory cells (A-Tregs) to acquire a gut-homing phenotype (α4β7+ CC chemokine receptor 9+) and the capacity to home to the lamina propria of the small intestine. Under conditions that favor the differentiation of A-Tregs (transforming growth factor-β1 and interleukin 2) in vitro, the inclusion of RA induces nearly all activated CD4+ T cells to express FoxP3 and greatly increases the accumulation of these cells. In the absence of RA, A-Treg differentiation is abruptly impaired by proficient antigen presenting cells or through direct co-stimulation. In the presence of RA, A-Treg generation occurs even in the presence of high levels of co-stimulation, with RA attenuating co-stimulation from interfering from FoxP3 induction. The recognition that RA induces gut imprinting, together with our finding that it enhances A-Treg conversion, differentiation, and expansion, indicates that RA production in vivo may drive both the imprinting and A-Treg development in the face of overt inflammation. JEM

Original languageEnglish
Pages (from-to)1765-1774
Number of pages10
JournalJournal of Experimental Medicine
Volume204
Issue number8
DOIs
StatePublished - 6 Aug 2007
Externally publishedYes

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