Helminth-induced regulation of T-cell transfer colitis requires intact and regulated T cell Stat6 signaling in mice

Infection with parasitic worms (helminths) alters host immune responses and can inhibit pathogenic inflammation. Helminth infection promotes a strong Th2 and T regulatory response while suppressing Th1 and Th17 function. Th2 responses are largely dependent on transcriptional programs directed by Stat6-signaling. We examined the importance of intact T cell Stat6 signaling on helminth-induced suppression of murine colitis that results from T cell transfer into immune-deficient mice. Colonization with the intestinal nematode Heligmosomoides polygyrus bakeri resolves WT T cell transfer colitis. However, if the transferred T cells lack intact Stat6 then helminth exposure failed to attenuate colitis or suppress MLN T cell IFN-gamma or IL17 production. Loss of Stat6 signaling resulted in decreased IL10 and increased IFN-gamma co-expression by IL-17(+) T cells. We also transferred T cells from mice with constitutive T cell expression of activated Stat6 (Stat6VT). These mice developed a severe eosinophilic colitis that also was not attenuated by helminth infection. These results show that T cell expression of intact but regulated Stat6 signaling is required for helminth infection-associated regulation of pathogenic intestinal inflammation.

Automated summary

Intact but regulated T cell expression of Stat6 signaling is crucial for the regulation of pathogenic intestinal inflammation associated with helminth infection. Loss of Stat6 signaling may result in colitis that is not attenuated by helminth exposure.