Format

Send to

Choose Destination
Immunity. 2008 Nov 14;29(5):758-70. doi: 10.1016/j.immuni.2008.09.018.

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

Author information

1
Section on Immunology and Immunogenetics, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.

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.

PMID:
19006694
PMCID:
PMC3140207
DOI:
10.1016/j.immuni.2008.09.018
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Secondary source ID, Grant support

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center