Journal article
c-Rel promotes type 1 and type 17 immune responses during Leishmania major infection
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-γ 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 naïve 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.
Language: | English |
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Publisher: | WILEY‐VCH Verlag |
Year: | 2011 |
Pages: | 1388-1398 |
ISSN: | 15214141 and 00142980 |
Types: | Journal article |
DOI: | 10.1002/eji.201041056 |
Animals Cell Differentiation Homeodomain Proteins IL-12 IL‐12 Interferon-gamma Interleukin-12 Interleukin-17 Interleukin-23 Leishmania major Leishmaniasis, Cutaneous Macrophages Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Proto-Oncogene Proteins c-rel RAG-1 protein T-Lymphocytes, Regulatory Th1 Th1 Cells Th17 Cells c-Rel c‐Rel myeloid cells