| First Author | Ma J | Year | 2012 |
| Journal | J Immunol | Volume | 188 |
| Issue | 11 | Pages | 5337-47 |
| PubMed ID | 22539794 | Mgi Jnum | J:188737 |
| Mgi Id | MGI:5441677 | Doi | 10.4049/jimmunol.1102979 |
| Citation | Ma J, et al. (2012) Protein kinase C-theta inhibits inducible regulatory T cell differentiation via an AKT-Foxo1/3a-dependent pathway. J Immunol 188(11):5337-47 |
| abstractText | Protein kinase C (PKC)-theta has been shown to be a critical TCR signaling molecule that promotes the activation and differentiation of naive T cells into inflammatory effector T cells. In this study, we demonstrate that PKC-theta-mediated signals inhibit inducible regulatory T cell (iTreg) differentiation via an AKT-Foxo1/3A pathway. TGF-beta-induced iTreg differentiation was enhanced in PKC-theta(-/-) T cells or wild-type cells treated with a specific PKC-theta inhibitor, but was inhibited by the PKC-theta activator PMA, or by CD28 crosslinking, which enhances PKC-theta activation. PKC-theta(-/-) T cells had reduced activity of the AKT kinase, and the expression of a constitutively active form of AKT in PKC-theta(-/-) T cells restored the ability to inhibit iTreg differentiation. Furthermore, knockdown or overexpression of the AKT downstream targets Foxo1 and Foxo3a was found to inhibit or promote iTreg differentiation in PKC-theta(-/-) T cells accordingly, indicating that the AKT-Foxo1/3A pathway is responsible for the inhibition of iTreg differentiation of iTregs downstream of PKC-theta. We conclude that PKC-theta is able to control T cell-mediated immune responses by shifting the balance between the differentiation of effector T cells and inhibitory Tregs. |
