Kofi
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 Posted: Mon Nov 17, 2008 8:22 am Post subject: Retinoic acid enhances regulatory T cell function |
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This may also partially account for the carcinogenic properties of
retinoic acid.
Immunity. 2008 Nov;29(5):758-70.
Retinoic Acid Enhances Foxp3 Induction Indirectly by Relieving
Inhibition from CD4(+)CD44(hi) Cells.
Hill JA, Hall JA, Sun CM, Cai Q, Ghyselinck N, Chambon P, Belkaid Y,
Mathis D, Benoist C.
Section on Immunology and Immunogenetics, Joslin Diabetes Center,
Department of Medicine, Brigham and Women>s Hospital, Harvard Medical
School, Boston, MA 02215, USA.
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 |
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