期刊
PLOS PATHOGENS
卷 12, 期 4, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.ppat.1005481
关键词
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资金
- Crohn's and Colitis Canada (CCC)
- Natural Sciences and Engineering Research Council (NSERC) of Canada
- Canadian Institutes for Health Research (CIHR)
- Alberta Innovates-Health Solutions (AI-HS)
- Canadian Association of Gastroenterology (CAG)/Janssen Inc.
- AI-HS
- CIHR/Canadian Digestive Health Foundation (CDHF) doctoral studentships
- Host-Parasite Interaction (HPI) program NSERC Canada
- Ciencias Sem Fronteiras CNPq Brazil
- AI-HS doctoral studentship
- Univ. Calgary Eyes High doctoral studentship
- Alberta Innovates [201000271] Funding Source: researchfish
Interleukin (IL)-22, an immune cell-derived cytokine whose receptor expression is restricted to non-immune cells (e.g. epithelial cells), can be anti-inflammatory and pro-inflammatory. Mice infected with the tapeworm Hymenolepis diminuta are protected from dinitrobenzene sulphonic acid (DNBS)-induced colitis. Here we assessed expulsion of H. diminuta, the concomitant immune response and the outcome of DNBS-induced colitis in wild-type (WT) and IL-22 deficient mice (IL-22(-/-)) +/- infection. Interleukin-22(-/-) mice had a mildly impaired ability to expel the worm and this correlated with reduced or delayed induction of TH2 immunity as measured by splenic and mesenteric lymph node production of IL-4, IL-5 and IL-13 and intestinal Muc-2 mRNA and goblet cell hyperplasia; in contrast, IL-25 increased in the small intestine of IL-22(-/-) mice 8 and 12 days post-infection compared to WT mice. In vitro experiments revealed that H. diminuta directly evoked epithelial production of IL-25 that was inhibited by recombinant IL-22. Also, IL-10 and markers of regulatory T cells were increased in IL-22(-/-) mice that displayed less DNBS (3 mg, ir. 72h)-induced colitis. Wild-type mice infected with H. diminuta were protected from colitis, as were infected IL-22(-/-) mice and the latter to a degree that they were almost indistinguishable from control, non-DNBS treated mice. Finally, treatment with anti-IL-25 antibodies exaggerated DNBS-induced colitis in IL-22(-/-) mice and blocked the anti-colitic effect of infection with H. diminuta. Thus, IL-22 is identified as an endogenous brake on helminth-elicited TH2 immunity, reducing the efficacy of expulsion of H. diminuta and limiting the effectiveness of the anti-colitic events mobilized following infection with H. diminuta in a non-permissive host.
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