| First Author | Pierau M | Year | 2009 |
| Journal | J Immunol | Volume | 183 |
| Issue | 10 | Pages | 6124-34 |
| PubMed ID | 19841181 | Mgi Jnum | J:157191 |
| Mgi Id | MGI:4430153 | Doi | 10.4049/jimmunol.0900246 |
| Citation | Pierau M, et al. (2009) Protein kinase B/Akt signals impair Th17 differentiation and support natural regulatory T cell function and induced regulatory T cell formation. J Immunol 183(10):6124-34 |
| abstractText | Protein kinase B (PKB)/Akt signals control T cell proliferation and differentiation but their effect on the generation and function of regulatory T cells (Treg) and Th17 cells is not well understood. In this study, we show that elevated PKB signals antagonize the immunosuppressive effect of TGF-beta1 on cell size, CD25 and CD98 expression, and proliferation of CD3-stimulated naive CD4(+) T cells from wild-type and CD28-deficient mice. Conventional CD4(+) T cells expressing active PKB are less susceptible to suppression by natural regulatory T cells. Although PKB signals do not affect the development of natural regulatory T cells, they enhance their suppressor capacity. Upon TCR triggering and TGF-beta1 costimulation, wild-type and CD28-deficient CD4(+) T cells transgenic for PKB readily express Foxp3, thereby acquiring suppressor capacity. These effects of elevated PKB signals on T cell function involve a marked and sustained activation of STAT5 and Foxp3 and reduction in nuclear NFATc1 levels. In contrast, PKB signals impair TGF-beta1/IL-6-mediated differentiation of naive CD4(+) T cells into the Th17 lineage. This correlates with an increased signaling of ERK, STAT5, and STAT6. Finally, elevated PKB signals reduced the severity of experimental autoimmune encephalomyelitis in wild-type mice but induced experimental autoimmune encephalomyelitis in mice deficient for CD28. Altogether, these data indicate an important role of PKB signals on control of TGF-beta1-mediated T cell responses and, thereby, on tolerizing and inflammatory immune processes. |
