| First Author | Britton GJ | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 2 | Pages | e0171547 |
| PubMed ID | 28158245 | Mgi Jnum | J:248422 |
| Mgi Id | MGI:5916542 | Doi | 10.1371/journal.pone.0171547 |
| Citation | Britton GJ, et al. (2017) Protein kinase C theta is required for efficient induction of IL-10-secreting T cells. PLoS One 12(2):e0171547 |
| abstractText | Secretion of interleukin-10 (IL-10) by CD4+ T cells is an essential immunoregulatory mechanism. The work presented here assesses the role of the signaling molecule protein kinase C theta (PKCtheta) in the induction of IL-10 expression in CD4+ T cells. Using wildtype and PKCtheta-deficient Tg4 T cell receptor transgenic mice, we implemented a well-described protocol of repeated doses of myelin basic protein (MBP)Ac1-9[4Y] antigen to induce Tr1-like IL-10+ T cells. We find that PKCtheta is required for the efficient induction of IL-10 following antigen administration. Both serum concentrations of IL-10 and the proportion of IL-10+ T cells were reduced in PKCtheta-deficient mice relative to wildtype mice following [4Y] treatment. We further characterized the T cells of [4Y] treated PKCtheta-deficient Tg4 mice and found reduced expression of the transcription factors cMaf, Nfil3 and FoxP3 and the surface receptors PD-1 and Tim3, all of which have been associated with the differentiation or function of IL-10+ T cells. Finally, we demonstrated that, unlike [4Y] treated wildtype Tg4 T cells, cells from PKCtheta-deficient mice were unable to suppress the priming of naive T cells in vitro and in vivo. In summary, we present data demonstrating a role for PKCtheta in the induction of suppressive, IL-10-secreting T cells induced in TCR-transgenic mice following chronic antigen administration. This should be considered when contemplating PKCtheta as a suitable drug target for inducing immune suppression and graft tolerance. |
