title: NKT Cell-Deficient Mice Harbor an Altered Microbiota That Fuels Intestinal Inflammation during Chemically Induced Colitis.
abstract: NKT cells are unconventional T cells that respond to self and microbe-derived lipid and glycolipid Ags presented by the CD1d molecule. Invariant NKT (iNKT) cells influence immune responses in numerous diseases. Although only a few studies have examined their role during intestinal inflammation, it appears that iNKT cells protect from Th1-mediated inflammation but exacerbate Th2-mediated inflammation. Studies using iNKT cell-deficient mice and chemically induced dextran sodium sulfate (DSS) colitis have led to inconsistent results. In this study, we show that CD1d-deficient mice, which lack all NKT cells, harbor an altered intestinal microbiota that is associated with exacerbated intestinal inflammation at steady-state and following DSS treatment. This altered microbiota, characterized by increased abundance of the bacterial phyla Proteobacteria, Deferribacteres, and TM7, among which the mucin-eating Mucispirillum, as well as members of the genus Prevotella and segmented filamentous bacteria, was transmissible upon fecal transplant, along with the procolitogenic phenotype. Our results also demonstrate that this proinflammatory microbiota influences iNKT cell function upon activation during DSS colitis. Collectively, alterations of the microbiota have a major influence on colitis outcome and therefore have to be accounted for in such experimental settings and in studies focusing on iNKT cells.
authors: Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors: Thirumahal
authors: 0000-0002-9771-1954
authors: T
authors: Selvanantham
authors: Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors: Qiaochu
authors: Q
authors: Lin
authors: Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors: Cynthia Xinyi
authors: 0000-0003-2106-1147
authors: CX
authors: Guo
authors: Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.|Centre for the Analysis of Genome Evolution and Function, University of Toronto, Toronto, Ontario M5S 3B2, Canada; and.
authors: Anuradha
authors: A
authors: Surendra
authors: Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors: Stephanie
authors: S
authors: Fieve
authors: Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors: Nichole K
authors: NK
authors: Escalante
authors: Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.|Centre for the Analysis of Genome Evolution and Function, University of Toronto, Toronto, Ontario M5S 3B2, Canada; and.
authors: David S
authors: 0000-0001-8479-3869
authors: DS
authors: Guttman
authors: Department of Laboratory Medicine and Pathology, University of Toronto and St. Michael's Hospital, Toronto, Ontario M5B 1W8, Canada.
authors: Catherine J
authors: CJ
authors: Streutker
authors: Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors: Susan J
authors: SJ
authors: Robertson
authors: Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors: Dana J
authors: DJ
authors: Philpott
authors: Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada; thierry.mallevaey@utoronto.ca.
authors: Thierry
authors: T
authors: Mallevaey
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D000069467:Fecal Microbiota Transplantation; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000473:pathology; D018720:Prevotella / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology
chemical_list: D016264:Dextran Sulfate