title: Nod1 Limits Colitis-Associated Tumorigenesis by Regulating IFN-γ Production.
abstract: Chronic intestinal inflammation is a major risk factor for the development of colorectal cancer. Nod1, a member of the Nod-like receptor (NLR) family of pattern recognition receptors, is a bacterial sensor that has been previously demonstrated to reduce susceptibility of mice to chemically induced colitis and subsequent tumorigenesis, but the mechanism by which it mediates its protection has not been elucidated. In this study, we show that Nod1 expression in the hematopoietic cell compartment is critical for limiting inflammation-induced intestinal tumorigenesis. Specifically, Nod1-deficient T cells exhibit impaired IFN-γ production during dextran sulfate sodium (DSS)-induced acute inflammation in vivo, and administration of the Nod1 ligand KF1B enhances IFN-γ responses by anti-CD3-activated T cells in vitro. Absence of IFN-γ signaling results in increased inflammation-associated tumors in mice, and adoptive transfer of Nod1(-/-) or IFNγ(-/-) T cells into T cell-deficient mice results in increased tumorigenesis as compared with T cell-deficient mice that were adoptively transferred with wild-type T cells. Collectively, these results suggest a previously unappreciated role for the innate immune receptor Nod1 in suppressing colitis-associated tumorigenesis through a T cell-mediated mechanism.
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109.
authors.forename: Sergey S
authors.identifier: 0000-0002-9241-4555
authors.initials: SS
authors.lastname: Seregin
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109.
authors.forename: Jiachen
authors.initials: J
authors.lastname: Chen
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109 gchenry@umich.edu.
authors.forename: Grace Y
authors.identifier: 0000-0001-6434-8696
authors.initials: GY
authors.lastname: Chen
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D063646:Carcinogenesis; D003092:Colitis / Q000139:chemically induced / Q000150:complications* / Q000276:immunology; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007113:Immunity, Innate; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D007422:Intestines / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053474:Nod1 Signaling Adaptor Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D053474:Nod1 Signaling Adaptor Protein; C507873:Nod1 protein, mouse; D007371:Interferon-gamma; D016264:Dextran Sulfate