title: Unique invariant natural killer T cells promote intestinal polyps by suppressing TH1 immunity and promoting regulatory T cells.
abstract: CD1d-restricted invariant natural killer T (iNKT) cells are known as potent early regulatory cells of immune responses. Besides the established roles in the regulation of inflammation and autoimmune disease, studies have shown that iNKT cells have important roles in tumor surveillance and the control of tumor metastasis. Here we found that the absence of iNKT cells markedly decreased the total number of intestinal polyps in APCMin/+mice, a model for colorectal cancer. Polyp iNKT cells were enriched for interleukin-10 (IL-10)- and IL-17-producing cells, showed a distinct phenotype being CD4+, NK1.1-CD44int, and PD-1lo, and they were negative for the NKT cell transcription factor promyelocytic leukemia zinc-finger. The absence of iNKT cells was associated with a reduced frequency of regulatory T (Tregs) cells and lower expression levels of FoxP3 protein and transcript uniquely in the polyps, and a switch to an inflammatory macrophage phenotype. Moreover, in iNKT cell-deficient APCMin/+mice, expression of T-helper (TH) 1-associated genes, such as IFN-γ and Nos2, was increased in polyps, concomitantly with elevated frequencies of conventional CD4+and CD8+T cells in this tissue. The results suggest that a population of regulatory iNKT cells locally promote intestinal polyp formation by enhancing Treg cells and immunosuppression of antitumor TH1 immunity.
authors.affiliation: Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Sedimbi
authors.affiliation: Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Löfbom
authors.affiliation: Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: A K
authors.initials: AK
authors.lastname: Singh
authors.affiliation: Department of Microbiology and Immunology and Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Porcelli
authors.affiliation: Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: S L
authors.initials: SL
authors.lastname: Cardell
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D000818:Animals; D015179:Colorectal Neoplasms / Q000276:immunology*; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000378:metabolism; D007422:Intestines / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics; D055611:Natural Killer T-Cells / Q000276:immunology*; D011127:Polyps / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C000613192:adenomatous polyposis coli protein, mouse; D007371:Interferon-gamma