Retinoic acid enhances Foxp3 induction indirectly by relieving inhibition from CD4+CD44hi Cells. - Archive ouverte HAL Access content directly
Journal Articles Immunity Year : 2008

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

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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.

Dates and versions

inserm-00350772 , version 1 (03-02-2009)

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Jonathan A. Hill, Jason A. Hall, Cheng-Ming Sun, Qi Cai, Norbert B. Ghyselinck, et al.. Retinoic acid enhances Foxp3 induction indirectly by relieving inhibition from CD4+CD44hi Cells.. Immunity, 2008, 29 (5), pp.758-70. ⟨10.1016/j.immuni.2008.09.018⟩. ⟨inserm-00350772⟩
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