title: P38 MAP kinase signaling is required for the conversion of CD4+CD25- T cells into iTreg.
abstract: CD4+CD25+ regulatory T cells (Treg) are important mediators of immune tolerance. A subset of Treg can be generated in the periphery by TGF-beta dependent conversion of conventional CD4+CD25- T cells into induced Treg (iTreg). In chronic viral infection or malignancy, such induced iTreg, which limit the depletion of aberrant or infected cells, may be of pathogenic relevance. To identify potential targets for therapeutic intervention, we investigated the TGF-beta signaling in Treg. In contrast to conventional CD4+ T cells, Treg exhibited marked activation of the p38 MAP kinase pathway. Inhibition of p38 MAP kinase activity prevented the TGF-beta-dependent conversion of CD4+CD25- T cells into Foxp3+ iTreg in vitro. Of note, the suppressive capacity of nTreg was not affected by inhibiting p38 MAP kinase. Our findings indicate that signaling via p38 MAP kinase seems to be important for the peripheral generation of iTreg; p38 MAP kinase could thus be a therapeutic target to enhance immunity to chronic viral infection or cancer.
authors.affiliation: I. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Samuel
authors.initials: S
authors.lastname: Huber
authors.forename: Jörg
authors.initials: J
authors.lastname: Schrader
authors.forename: Gerhard
authors.initials: G
authors.lastname: Fritz
authors.forename: Katrin
authors.initials: K
authors.lastname: Presser
authors.forename: Steffen
authors.initials: S
authors.lastname: Schmitt
authors.forename: Ari
authors.initials: A
authors.lastname: Waisman
authors.forename: Stefan
authors.initials: S
authors.lastname: Lüth
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
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015704:CD4 Antigens / Q000276:immunology*; D005434:Flow Cytometry; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D051379:Mice; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D048051:p38 Mitogen-Activated Protein Kinases