Unknown

Dataset Information

0

Retinoic acid enhances Foxp3 induction indirectly by relieving inhibition from CD4+CD44hi Cells.


ABSTRACT: CD4(+)Foxp3(+) regulatory T (Treg) cells originate primarily from thymic differentiation, but conversion of mature T lymphocytes to Foxp3 positivity can be elicited by several means, including in vitro activation in the presence of TGF-beta. Retinoic acid (RA) increases TGF-beta-induced expression of Foxp3, through unknown molecular mechanisms. We showed here that, rather than enhancing TGF-beta signaling directly in naive CD4(+) T cells, RA negatively regulated an accompanying population of CD4(+) T cells with a CD44(hi) memory and effector phenotype. These memory cells actively inhibited the TGF-beta-induced conversion of naive CD4(+) T cells through the synthesis of a set of cytokines (IL-4, IL-21, IFN-gamma) whose expression was coordinately curtailed by RA. This indirect effect was evident in vivo and required the expression of the RA receptor alpha. Thus, cytokine-producing CD44(hi) cells actively restrain TGF-beta-mediated Foxp3 expression in naive T cells, and this balance can be shifted or fine-tuned by RA.

SUBMITTER: Hill JA 

PROVIDER: S-EPMC3140207 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications

Retinoic acid enhances Foxp3 induction indirectly by relieving inhibition from CD4+CD44hi Cells.

Hill Jonathan A JA   Hall Jason A JA   Sun Cheng-Ming CM   Cai Qi Q   Ghyselinck Norbert N   Chambon Pierre P   Belkaid Yasmine Y   Mathis Diane D   Benoist Christophe C  

Immunity 20081101 5


CD4(+)Foxp3(+) regulatory T (Treg) cells originate primarily from thymic differentiation, but conversion of mature T lymphocytes to Foxp3 positivity can be elicited by several means, including in vitro activation in the presence of TGF-beta. Retinoic acid (RA) increases TGF-beta-induced expression of Foxp3, through unknown molecular mechanisms. We showed here that, rather than enhancing TGF-beta signaling directly in naive CD4(+) T cells, RA negatively regulated an accompanying population of CD4  ...[more]

Similar Datasets

2008-11-16 | E-GEOD-13306 | biostudies-arrayexpress
2008-11-16 | GSE13306 | GEO
| S-EPMC4424416 | biostudies-literature
| S-EPMC2214761 | biostudies-literature
| S-EPMC4724573 | biostudies-literature
| S-EPMC3258871 | biostudies-other
| S-EPMC3178710 | biostudies-literature
2006-01-23 | GSE4075 | GEO
| S-EPMC207565 | biostudies-literature
| S-EPMC4757416 | biostudies-literature