期刊
SCIENTIFIC REPORTS
卷 7, 期 -, 页码 -出版社
NATURE RESEARCH
DOI: 10.1038/srep40631
关键词
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资金
- Natural Sciences and Engineering Research Council of Canada (NSERC) grant
- National Sciences and Engineering Research Council (NSERC)-CREATE Host-Parasite Interactions program of the University of Calgary
- CIHR-Canadian Association of Gastroenterology (CAG)/Allergan Inc.
- AI-HS post-doctoral fellowships
- Eyes High post-doctoral fellowship from the Univ. Calgary
- Alberta Innovates [201500767, 201000271] Funding Source: researchfish
Infection with helminth parasites has been explored as a treatment for autoimmune and inflammatory diseases. As helminth antigens have potent immunomodulation properties capable of inducing regulatory programs in a variety of cell types, transferring cells treated with helminth antigens represents a novel extension to helminth therapy. Previous work determined that transfer of bone marrow-derived dendritic cells (DC) pulsed with a crude extract of the tapeworm Hymenolepis diminuta (HD) can suppress colitis in recipient mice. The present study explored the mechanism of disease suppression and the importance of interleukin (IL)-4 signaling. Transfer of HD-DCs suppressed dinitrobenzene sulfonic acid (DNBS)-induced colitis through activation of recipient IL-4 receptor-alpha. The transferred HD-DCs required IL-4R alpha and the capacity to secrete IL-10 to drive IL-4 and IL-10 production and to suppress colitis in recipient mice. Treatment of DCs with IL-4 evokes an alternatively activated phenotype, but adoptive transfer of these cells did not affect the outcome of colitis. Collectively, these studies demonstrate the complexity between IL-4 and IL-10 in donor cells and recipient, and the requirement for parasite-and host-derived factors in this novel form of cell therapy. Thus IL-4Ra signaling is revealed as a pathway that could be exploited for helminth antigen cell-based therapy.
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