title: Runx3 is required for full activation of regulatory T cells to prevent colitis-associated tumor formation.
abstract: Inflammation is increasingly recognized as an essential component of tumorigenesis, which is promoted and suppressed by various T cell subsets acting in different ways. It was shown previously in Runx3-deficient mice that differentiation of CD8 T and NK cells is perturbed. In this study, we show that Runx3 is also required for proper differentiation and function of regulatory T cells. In Runx3-deficient mice, T cells were unable to inhibit inflammation and to suppress tumor development. As expected, recombination activating gene 2-deficient mice bearing Runx3-deficient lymphocytes spontaneously developed colon tumors. However, tumor formation was completely blocked by transfer of either regulatory T cells or CD8 T cells derived from wild-type mice to mutant mice or by housing mutant mice in a specific pathogen-free condition. These results indicate that Runx3-deficient lymphocytes and microorganisms act together to induce inflammation and consequently induce the development of colon tumors.
authors.affiliation: Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Sugai
authors.forename: Koji
authors.initials: K
authors.lastname: Aoki
authors.forename: Motomi
authors.initials: M
authors.lastname: Osato
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nambu
authors.forename: Kosei
authors.initials: K
authors.lastname: Ito
authors.forename: Makoto M
authors.initials: MM
authors.lastname: Taketo
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D003092:Colitis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D003106:Colon / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D050677:Core Binding Factor Alpha 3 Subunit / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D005756:Gastritis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; C493730:Runx3 protein, mouse