Control of Schistosoma mansoni egg‐induced inflammation by IL‐4‐responsive CD4+CD25−CD103+Foxp3− cells is IL‐10‐dependent
Copyright policy )Control of Schistosoma mansoni egg‐induced inflammation by IL‐4‐responsive CD4+CD25−CD103+Foxp3− cells is IL‐10‐dependent
AbstractHost protection to helminth infection requires IL‐4 receptor α chain (IL‐4Rα) signalling and the establishment of finely regulated Th2 responses. In the current 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‐4Rα‐deficient BALB/c mice (iLckcreIl4ra−/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‐4Rα‐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‐4Rα‐responsive CD4+CD25−CD103+ cells, but not CD4+CD25high or CD4+CD25−CD103− cells, controlled inflammation in iLckcreIl4ra−/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.
- University of Liège Belgium
- University of Cape Town South Africa
- International Centre for Genetic Engineering and Biotechnology Italy
CD4-Positive T-Lymphocytes, Receptors, Cell Surface, Sciences de la santé humaine, Immunologie & maladie infectieuse, Mice, Antigens, CD, Animals, Immunology & infectious disease, Human health sciences, Mice, Knockout, Mice, Inbred BALB C, Reverse Transcriptase Polymerase Chain Reaction, Interleukin-2 Receptor alpha Subunit, Forkhead Transcription Factors, Schistosoma mansoni, Flow Cytometry, Schistosomiasis mansoni, Interleukin-10, Mice, Inbred C57BL, FoxP3+ Treg cells, CD103, RNA, Interleukin-4, Lymph Nodes, Integrin alpha Chains, IL-4 receptor alpha chain, Signal Transduction
CD4-Positive T-Lymphocytes, Receptors, Cell Surface, Sciences de la santé humaine, Immunologie & maladie infectieuse, Mice, Antigens, CD, Animals, Immunology & infectious disease, Human health sciences, Mice, Knockout, Mice, Inbred BALB C, Reverse Transcriptase Polymerase Chain Reaction, Interleukin-2 Receptor alpha Subunit, Forkhead Transcription Factors, Schistosoma mansoni, Flow Cytometry, Schistosomiasis mansoni, Interleukin-10, Mice, Inbred C57BL, FoxP3+ Treg cells, CD103, RNA, Interleukin-4, Lymph Nodes, Integrin alpha Chains, IL-4 receptor alpha chain, Signal Transduction
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