| First Author | Reinhard K | Year | 2011 |
| Journal | Eur J Immunol | Volume | 41 |
| Issue | 5 | Pages | 1388-98 |
| PubMed ID | 21469108 | Mgi Jnum | J:175407 |
| Mgi Id | MGI:5285491 | Doi | 10.1002/eji.201041056 |
| Citation | Reinhard K, et al. (2011) c-Rel promotes type 1 and type 17 immune responses during Leishmania major infection. Eur J Immunol 41(5):1388-98 |
| abstractText | Recent studies demonstrated the crucial role of c-Rel in directing Treg lineage commitment and its involvement in T helper 1 (Th1) cell-mediated autoimmune inflammation. We thus wondered whether these opposite functions of c-Rel influence the course of antiparasitic immune responses against Leishmania major, an accepted model for the impact of T-cell subsets on disease outcome. Here we show that c-Rel-deficient (rel(-/-) ) mice infected with L. major displayed dramatically exacerbated leishmaniasis and enhanced parasite burdens. In contrast to WT mice, IFN-gamma and IL-17 production in response to L. major antigens was severely impaired in rel(-/-) mice. Reconstitution of Rag1(-/-) T-cell deficient mice with rel(-/-) CD4(+) T cells followed by L. major infection demonstrated that c-Rel-deficient T cells mount normal Th1 responses and are able to contain the infection. Similarly, Th1 differentiation of naive CD4(+) cells in vitro was normal. Notably, a selective defect in IL-12 and IL-23 production was observed in rel(-/-) DCs compared with their WT counterparts. In conclusion, our data suggest that the expression of c-Rel in myeloid cells is essential for clearance of L. major and that this c-Rel-mediated effect is dominant over the lack of Tregs. |
