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United States Department of Agriculture

Agricultural Research Service

Title: Heligmosomoides Polygyrus Inhibits Established Colitis in Il-10 Deficient Mice

Authors
item Elliott, David - UNIVERSITY OF IOWA
item Setiawan, Tommy - " "
item Metwali, Ahmed - " "
item Blum, Arthur - " "
item Urban, Joseph
item Weinstock, Joel - UNIVERSITY OF IOWA

Submitted to: European Journal of Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 1, 2004
Publication Date: October 30, 2004
Citation: Elliott, D.E., Setiawan T., Metwali, A., Blum, A., Urban, Jr., J.F., Weinstock, J.V. 2004. Heligmosomoides polygyrus inhibites established colitis in IL-10 deficient mice. European Journal of Immunology. 34:2690-2696.

Interpretive Summary: Mouse models of inflammatory bowel disease (IBD) have shown that infection with worms can prevent or ameliorate colitis. These experimental models were designed to test the hypothesis that humans from industrialized Western countries with few worm infections express immune pathology that results in increased expression of IBD compared to lesser developed countries where worm infections are common and IBD is infrequent. The current studies use a mouse model that give consistent and spontaneous expression of colitis in a genetically deficient animal, and show that concurrent parasitic worm infection reduces the severity of the disease. It is also demonstrated that lymphocytes from infected mice can transfer the protective response to naïve mice that are expression colitis. These results demonstrate that there are regulatory cells that control the intensity of the disease. They also suggest that therapy, including dietary manipulation, can be used to promote the activity of these regulatory cells which could improve disease outcome or therapeutic efficacy. This work is important to scientists and clinicians that explore treatment and prophylactic procedures to correct intestinal disorders and the absorption of nutrients from the intestine. The impact will be related to better control procedures for inflammatory diseases of the intestine

Technical Abstract: Inflammatory bowel disease (IBD) is prevalent in industrialized countries, but rare in less developed countries. Helminths, common in less developed countries, may induce immune regulatory circuits protecting from IBD. This study was to determine how intestinal helminths may afford protection. IL10-/- mice given piroxicam develop severe and persistent colitis. Colonization of piroxicam-treated colitic IL10-/- mice with H. polygyrus (an intestinal helminth) suppressed established inflammation. LPMC from colitic IL10-/- mice without H. polygyrus released IFNg and IL12. This Th1 cytokine production was impaired in mice bearing H. polygyrus. H. polygyrus augmented mucosal IL13 but not IL4 or IL5 production. Transfer of MLN T cells from IL10-/- animals harboring H. polygyrus into colitic IL10-/- recipients was sufficient to inhibit colitis. Conclusion: H. polygyrus inhibits ongoing IL10-/- colitis and mucosal Th1 cytokine production through induction of regulatory T cells. These regulatory T cells may be unique, since they control intestinal inflammation without IL10.

Last Modified: 7/28/2014
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