MAP kinase p38 and its relation to T cell anergy and suppressor function of regulatory T cells.
Diverse regulatory T cell populations (Treg) are important for the control of self tolerance and immune homeostasis. These include naturally occurring CD4+CD25+ Treg (nTreg) and induced Treg (iTreg). Tolerogenic dendritic cells, modulated by IL-10, are able to convert peripheral T cells into iTreg. These are anergic and characterized by a G(1) cell cycle arrest, dependent on elevated levels of the cdk inhibitor p27(Kip1). Novel data revealed a distinct pattern of MAP kinase activation in iTreg different from clonal T cell anergy, with enhanced activation of the p38-MAPKAP-K2/3 pathway. p38 is involved in cell cycle control and its activity is a prerequisite for the induction and maintenance of the anergic state in iTreg. Inhibition of p38 leads to down regulation of p27(Kip1), cell cycle progress and loss of regulatory T cell function. Here, we discuss these data in light of the role of p38 and p27(Kip1) in T cell activation, anergy induction and cell cycle control.
Adler
Henric S
HS
Department of Dermatology, University of Mainz, Mainz, Germany.
Steinbrink
Kerstin
K
D000818:Animals; D002453:Cell Cycle; D017635:Clonal Anergy; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D006801:Humans; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D050760:Cyclin-Dependent Kinase Inhibitor p27; D048051:p38 Mitogen-Activated Protein Kinases