title: Activin a promotes the TGF-beta-induced conversion of CD4+CD25- T cells into Foxp3+ induced regulatory T cells.
abstract: 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.
authors.affiliation: Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Samuel
authors.initials: S
authors.lastname: Huber
authors.forename: Felix R
authors.initials: FR
authors.lastname: Stahl
authors.forename: Jörg
authors.initials: J
authors.lastname: Schrader
authors.forename: Stefan
authors.initials: S
authors.lastname: Lüth
authors.forename: Katrin
authors.initials: K
authors.lastname: Presser
authors.forename: Antonella
authors.initials: A
authors.lastname: Carambia
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Sabine
authors.initials: S
authors.lastname: Werner
authors.forename: Manfred
authors.initials: M
authors.lastname: Blessing
authors.forename: Johannes
authors.initials: J
authors.lastname: Herkel
authors.forename: Christoph
authors.initials: C
authors.lastname: Schramm