Activin a promotes the TGF-beta-induced conversion of CD4+CD25- T cells into Foxp3+ induced regulatory T cells.
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Activin a promotes the TGF-beta-induced conversion of CD4+CD25- T cells into Foxp3+ induced regulatory T cells. / Huber, Samuel; Stahl, Felix R; Schrader, Jörg; Lüth, Stefan; Presser, Katrin; Carambia, Antonella; Flavell, Richard A; Werner, Sabine; Blessing, Manfred; Herkel, Johannes; Schramm, Christoph.
In: J IMMUNOL, Vol. 182, No. 8, 8, 2009, p. 4633-4640.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Activin a promotes the TGF-beta-induced conversion of CD4+CD25- T cells into Foxp3+ induced regulatory T cells.
AU - Huber, Samuel
AU - Stahl, Felix R
AU - Schrader, Jörg
AU - Lüth, Stefan
AU - Presser, Katrin
AU - Carambia, Antonella
AU - Flavell, Richard A
AU - Werner, Sabine
AU - Blessing, Manfred
AU - Herkel, Johannes
AU - Schramm, Christoph
PY - 2009
Y1 - 2009
N2 - TGF-beta induces the conversion of CD4(+)CD25(-) T cells into CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg). Activin A is a pleiotropic TGF-beta family member and is expressed in response to inflammatory signals. In this study, we report on the effects of activin A on the conversion of CD4(+)CD25(-) T cells into Foxp3-expressing induced Treg (iTreg). Activin A was able to promote the conversion of CD4(+)CD25(-) T cells into iTreg in a dose-dependent manner in vitro. Activin A together with TGF-beta1 had synergistic effects on the rate of iTreg conversion in vitro. Intact TGF-beta1 signaling seemed to be essential for the effects of activin A on iTreg generation because cells overexpressing a dominant negative TGF-beta type II receptor could not be converted by activin A in vitro. In vivo, the frequency of peripheral, but not central, Treg was increased in transgenic mice with elevated activin A serum levels and the in vivo conversion rate of CD4(+)CD25(-) T cells into Foxp3-expressing iTreg was increased as compared with wild type mice. These data suggest a role for activin A as a promoter of the TGF-beta dependent conversion of CD4(+)CD25(-) T cells into iTreg in vitro and in vivo. Therefore, besides promoting inflammation, activin A may contribute to the regulation of inflammation via the expansion of peripheral Treg.
AB - TGF-beta induces the conversion of CD4(+)CD25(-) T cells into CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg). Activin A is a pleiotropic TGF-beta family member and is expressed in response to inflammatory signals. In this study, we report on the effects of activin A on the conversion of CD4(+)CD25(-) T cells into Foxp3-expressing induced Treg (iTreg). Activin A was able to promote the conversion of CD4(+)CD25(-) T cells into iTreg in a dose-dependent manner in vitro. Activin A together with TGF-beta1 had synergistic effects on the rate of iTreg conversion in vitro. Intact TGF-beta1 signaling seemed to be essential for the effects of activin A on iTreg generation because cells overexpressing a dominant negative TGF-beta type II receptor could not be converted by activin A in vitro. In vivo, the frequency of peripheral, but not central, Treg was increased in transgenic mice with elevated activin A serum levels and the in vivo conversion rate of CD4(+)CD25(-) T cells into Foxp3-expressing iTreg was increased as compared with wild type mice. These data suggest a role for activin A as a promoter of the TGF-beta dependent conversion of CD4(+)CD25(-) T cells into iTreg in vitro and in vivo. Therefore, besides promoting inflammation, activin A may contribute to the regulation of inflammation via the expansion of peripheral Treg.
M3 - SCORING: Zeitschriftenaufsatz
VL - 182
SP - 4633
EP - 4640
JO - J IMMUNOL
JF - J IMMUNOL
SN - 0022-1767
IS - 8
M1 - 8
ER -
