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Publication : IL-33, a potent inducer of adaptive immunity to intestinal nematodes.

First Author  Humphreys NE Year  2008
Journal  J Immunol Volume  180
Issue  4 Pages  2443-9
PubMed ID  18250453 Mgi Jnum  J:131991
Mgi Id  MGI:3774910 Doi  10.4049/jimmunol.180.4.2443
Citation  Humphreys NE, et al. (2008) IL-33, a potent inducer of adaptive immunity to intestinal nematodes. J Immunol 180(4):2443-9
abstractText  IL-33 (IL-1F11) binds ST2 (IL-1R4), both of which are associated with optimal CD4(+) Th2 polarization. Exogenous IL-33 drives induction of Th2-associated cytokines and associated pathological changes within the gut mucosa. Th2 polarization is also a prerequisite to expulsion of the intestinal-dwelling nematode Trichuris muris. In this study, we demonstrate that IL-33 mRNA is expressed early during parasite infection and susceptible mice can be induced to expel the parasite by a regime of exogenous IL-33 administration. IL-33 prevents an inappropriate parasite-specific Th1-polarized response and induces IL-4, IL-9, and IL-13. This redirection requires the presence of T cells and must occur at the initiation of the response to the pathogen. Interestingly, exogenous IL-33 also induced thymic stromal lymphopoietin mRNA within the infected caecum, an epithelial cell-restricted cytokine essential for the generation of Th2-driven parasite immunity. IL-33 also acts independently of T cells, altering intestinal pathology in chronically infected SCID mice, leading to an increased crypt length and intestinal epithelial cell proliferation, but reducing goblet cell hyperplasia. Thus, the ability of IL-33 to induce Th2 responses has functional relevance in the context of intestinal helminth infection, particularly during the initiation of the response.
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