| First Author | Jirmanova L | Year | 2007 |
| Journal | J Immunol | Volume | 178 |
| Issue | 7 | Pages | 4153-8 |
| PubMed ID | 17371971 | Mgi Jnum | J:145060 |
| Mgi Id | MGI:3833219 | Doi | 10.4049/jimmunol.178.7.4153 |
| Citation | Jirmanova L, et al. (2007) Gadd45alpha regulates p38-dependent dendritic cell cytokine production and Th1 differentiation. J Immunol 178(7):4153-8 |
| abstractText | Gadd45alpha inhibits the activation of p38 by the T cell alternative pathway involving phosphorylation of p38 Tyr(323). Given that T cell p38 may play a role in Th1 development, the response to Th-skewing Ags was analyzed in Gadd45alpha(-/-) mice. Despite constitutively increased p38 activity in Gadd45alpha(-/-) T cells, the Th1 immune response to Toxoplasma gondii Ag (STAg), was diminished. In contrast to T cells, dendritic cells (DC) lacked the alternative p38 activation pathway. Gadd45alpha(-/-) DCs responded to STAg with low levels of MAP kinase cascade-dependent p38 activation, IL-12 production, and CD40 expression. Wild-type T cells transferred into Gadd45alpha(-/-) recipients had a diminished Th1 response to STAg, whereas Gadd45alpha(-/-) T cells transferred into wild-type hosts behaved normally. Therefore, Gadd45alpha has tissue-specific and opposing functions on p38 activity, and Gadd45alpha-regulated p38 activation in DCs is a critical event in Th1 polarization in vivo. |
