Control of Schistosoma mansoni egg-induced inflammation by IL-4-responsive CD4+CD25−CD103+Foxp3− cells is IL-10-dependent

Dewals, Benjamin G; Hoving, Jennifer C.; Horsnell, William G.C.; Brombacher, Frank

doi:10.1002/eji.200940075

Article (Scientific journals)

Control of Schistosoma mansoni egg-induced inflammation by IL-4-responsive CD4+CD25−CD103+Foxp3− cells is IL-10-dependent

Dewals, Benjamin G; Hoving, Jennifer C.; Horsnell, William G.C. et al.

2010 • In European Journal of Immunology, 40, p. 2837-2847

Peer Reviewed verified by ORBi

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https://hdl.handle.net/2268/69056

DOI
10.1002/eji.200940075

PubMed
20821727

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Keywords :

CD103; FoxP3+ Treg cells; IL-4 receptor alpha chain; Schistosoma mansoni

Abstract :

[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

Publication date :

2010

Journal title :

European Journal of Immunology

ISSN :

0014-2980

eISSN :

1521-4141

Publisher :

VCH Verlagsgesellschaft, Weinheim, Germany

Volume :

Pages :

2837-2847

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 13 August 2010

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