| First Author | Chang X | Year | 2011 |
| Journal | Immunity | Volume | 34 |
| Issue | 2 | Pages | 201-12 |
| PubMed ID | 21333552 | Mgi Jnum | J:168978 |
| Mgi Id | MGI:4939508 | Doi | 10.1016/j.immuni.2011.01.017 |
| Citation | Chang X, et al. (2011) The Kinases MEKK2 and MEKK3 Regulate Transforming Growth Factor-beta-Mediated Helper T Cell Differentiation. Immunity 34(2):201-12 |
| abstractText | Mitogen-activated protein kinases (MAPKs) are key mediators of the T cell receptor (TCR) signals but their roles in T helper (Th) cell differentiation are unclear. Here we showed that the MAPK kinase kinases MEKK2 (encoded by Map3k2) and MEKK3 (encoded by Map3k3) negatively regulated transforming growth factor-beta (TGF-beta)-mediated Th cell differentiation. Map3k2(-/-)Map3k3(Lck-Cre/-) mice showed an abnormal accumulation of regulatory T (Treg) and Th17 cells in the periphery, consistent with Map3k2(-/-)Map3k3(Lck-Cre/-) naive CD4(+) T cells' differentiation into Treg and Th17 cells with a higher frequency than wild-type (WT) cells after TGF-beta stimulation in vitro. In addition, Map3k2(-/-)Map3k3(Lck-Cre/-) mice developed more severe experimental autoimmune encephalomyelitis. Map3k2(-/-)Map3k3(Lck-Cre/-) T cells exhibited impaired phosphorylation of SMAD2 and SMAD3 proteins at their linker regions, which negatively regulated the TGF-beta responses in T cells. Thus, the crosstalk between TCR-induced MAPK and the TGF-beta signaling pathways is important in regulating Th cell differentiation. |
