| First Author | Dewals B | Year | 2010 |
| Journal | Eur J Immunol | Volume | 40 |
| Issue | 10 | Pages | 2837-47 |
| PubMed ID | 20821727 | Mgi Jnum | J:165816 |
| Mgi Id | MGI:4838496 | Doi | 10.1002/eji.200940075 |
| Citation | Dewals B, et al. (2010) Control of Schistosoma mansoni egg-induced inflammation by IL-4-responsive CD4(+)CD25(-)CD103(+)Foxp3(-) cells is IL-10-dependent. Eur J Immunol 40(10):2837-47 |
| abstractText | Host protection to helminth infection requires IL-4 receptor alpha chain (IL-4Ralpha) signalling and the establishment of finely regulated Th2 responses. In the current study, the role of IL-4Ralpha-responsive T cells in Schistosoma mansoni egg-induced inflammation was investigated. Egg-induced inflammation in IL-4Ralpha-responsive BALB/c mice was accompanied with Th2-biased responses, whereas T-cell-specific IL-4Ralpha-deficient BALB/c mice (iLck(cre)Il4ra(-) (/lox)) developed Th1-biased responses with heightened inflammation. The proportion of Foxp3(+) Treg in the draining LN of control mice did not correlate with the control of inflammation and was reduced in comparison to T-cell-specific IL-4Ralpha-deficient mice. This was due to IL-4-mediated inhibition of CD4(+)Foxp3(+) Treg 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-4Ralpha-responsive CD4(+)CD25(-)CD103(+) cells, but not CD4(+)CD25(high) or CD4(+)CD25(-)CD103(-) cells, controlled inflammation in iLck(cre)Il4ra(-) (/lox) mice. 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(+) Treg in vivo and promotes CD4(+)CD25(-)CD103(+)Foxp3(-) cells that control S. mansoni egg-induced inflammation via IL-10. |
