Heligmosomoides polygyrus inhibits established colitis in IL-10-deficient mice.
Inflammatory bowel disease (IBD) is prevalent in industrialized countries, but rare in less-developed countries. Helminths, common in less-developed countries, may induce immunoregulatory circuits protective against IBD. IL-10(-/-) mice given piroxicam develop severe and persistent colitis. Lamina propria mononuclear cells from colitic IL-10(-/-) mice released IFN-gamma and IL-12. The ongoing piroxicam-induced colitis could be partially blocked with anti-IL-12 monoclonal antibody suggesting that the inflammation was at least partly IL-12 dependent. Colonization of piroxicam-treated colitic IL-10(-/-) mice with Heligmosomoides polygyrus (an intestinal helminth) suppressed established inflammation and inhibited mucosal IL-12 and IFN-gamma production. H. polygyrus augmented mucosal IL-13, but not IL-4 or IL-5 production. Transfer of mesenteric lymph node (MLN) T cells from IL-10(-/-) animals harboring H. polygyrus into colitic IL-10(-/-) recipients inhibited colitis. MLN T cells from worm-free mice did not. Foxp3 (scurfin) drives regulatory T cell function. H. polygyrus enhanced Foxp3 mRNA expression in MLN T cells that had regulatory activity. This suggests that H. polygyrus inhibits ongoing IL-10(-/-) colitis in part through blocking mucosal Th1 cytokine production. Resolution of inflammation is associated with increased IL-13 production and can be adoptively transferred by MLN T cells.
Elliott
David E
DE
Department of Internal Medicine, Division of Gastroenterology-Hepatology, University of Iowa College of Medicine, Iowa City, IA 52242, USA. david-elliott@uiowa.edu
Setiawan
Tommy
T
Metwali
Ahmed
A
Blum
Arthur
A
Urban
Joseph F
JF
Weinstock
Joel V
JV
D019264:Adoptive Transfer; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000172:deficiency* / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology; D051379:Mice; D009351:Nematospiroides dubius / Q000276:immunology; D010894:Piroxicam / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D017206:Strongylida Infections / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology* / Q000382:microbiology
D016861:Cyclooxygenase Inhibitors; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D012333:RNA, Messenger; D016753:Interleukin-10; D010894:Piroxicam; D018664:Interleukin-12; D007371:Interferon-gamma