[en] Host protection to helminth infection requires IL-4Rα signalling and the establishment of finely regulated Th2 responses. In the present study, the role of IL-4Rα-responsive T cells in Schistosoma mansoni egg-induced inflammation was investigated. Egg-induced inflammation in IL-4Rα-responsive BALB/c mice was accompanied with Th2-biased responses, whereas T cell-specific IL-4R-deficient BALB/c mice (iLckcreIl4ra−/lox) developed Th1-biased responses with heightened inflammation. The proportion of Foxp3+ Tregs in the draining lymph node of control mice did not correlate with the control of inflammation and was reduced in comparison to T cell-specific IL-4R-deficient mice. This was due to IL-4-mediated inhibition of CD4+Foxp3+ Tregs conversion, demonstrated in adoptively transferred Rag2−/− mice. Interestingly, reduced footpad swelling in Il4ra−/lox mice was associated with the induction of IL-4 and IL-10-secreting CD4+CD25−CD103+Foxp3− cells, confirmed in S. mansoni infection studies. Transfer of IL-4Rα-responsive CD4+CD25−CD103+ cells, but not CD4+CD25high or CD4+CD25−CD103− cells, controlled inflammation in iLckcreIl4ra−/lox mice. It finally turned out that the control of inflammation depended on IL-10, as transferred CD4+CD25−CD103+ cells from IL-10-deficient mice were not able to effectively downregulate inflammation. Together, these results demonstrate that IL-4 signalling in T cells inhibits Foxp3+ Tregs in vivo and promotes CD4+CD25−CD103+Foxp3− cells that control S. mansoni egg-induced inflammation via IL-10.
Disciplines :
Immunology & infectious disease
Author, co-author :
Dewals, Benjamin G ; Université de Liège - ULiège > Immunologie et vaccinologie
Hoving, Jennifer C.
Horsnell, William G.C.
Brombacher, Frank
Language :
English
Title :
Control of Schistosoma mansoni egg-induced inflammation by IL-4-responsive CD4+CD25−CD103+Foxp3− cells is IL-10-dependent
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