|Elliott, David -|
|Metwali, A -|
|Leung, J -|
|Setiawan, T -|
|Blum, A -|
|Ince, M -|
|Bazzone, L -|
|Stadecker, M -|
|Weinstock, Josel -|
Submitted to: Journal of Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: June 15, 2008
Publication Date: August 15, 2008
Citation: Elliott, D.E., Metwali, A., Leung, J., Setiawan, T., Blum, A.M., Ince, M.N., Bazzone, L.E., Stadecker, M.J., Urban Jr, J.F., Weinstock, J.V. 2008. Colonization with Heligmosomoides polygyrus suppresses mucosal IL-17 production. Journal of Immunology. 181(4):2414-2419. Interpretive Summary: Mouse models of inflammatory bowel disease (IBD) demonstrated 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 to study regulation of IBD by a unique population of T cells that produce the cytokine IL-17 that is the basis of many autoimmune diseases. It was observed that mice infected with the worm parasite, Heligmosomoides polygyrus, reduced expression of the gene product for IL-17, but augmented productions of cytokines IL-4 and IL-10 that reduce the level of inflammation. These results demonstrated that targeting cells that produce IL-17 can control the intensity of the disease. They also suggest that therapy, including dietary manipulation, can be used to promote the activity of other cytokines that could improve disease outcome. 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: Helminth exposure appears to protect hosts from inappropriate inflammatory responses, such as those causing inflammatory bowel disease. A recently identified, strongly pro-inflammatory limb of the immune response is characterized by T cell IL-17 production. Many autoimmune-type inflammatory diseases are associated with IL-17 release. Because helminths protect from these diseases, we examined IL-17 production in helminth-colonized mice. We colonized mice with Heligmosomoides polygyrus, an intestinal helminth, and analyzed IL-17 production by lamina propria mononuclear cells (LPMC) and mesenteric lymph node (MLN) cells. Colonization with H. polygyrus reduced IL-17A mRNA by MLN cells and inhibited IL-17 production by cultured LPMC and MLN cells. Helminth exposure augmented IL-4 and IL-10 production. Blocking both IL-4 and IL-10, but not IL-10 alone, restored IL-17 production in vitro. Colonization of colitic IL-10-deficient mice with H. polygyrus suppresses LPMC IL-17 production and improves colitis. Ab-mediated blockade of IL-17 improves colitis in IL-10-deficient mice. Thus, helminth-associated inhibition of IL-17 production is most likely an important mechanism mediating protection from inappropriate intestinal inflammation.