title: IL-13Rα2-bearing, type II NKT cells reactive to sulfatide self-antigen populate the mucosa of ulcerative colitis.
abstract: OBJECTIVE
  Previous studies have shown that ulcerative colitis (UC) is associated with the presence of lamina propria non-invariant (Type II) NKT cells producing IL-13 and mediating epithelial cell cytotoxicity. Here we sought to define the antigen(s) stimulating the NKT cells and to quantitate these cells in the UC lamina propria.
  
  
  METHODS
  Detection of Type II NKT cells in UC lamina propria mononuclear cells (LPMC) with lyso-sulfatide loaded tetramer and quantum dot-based flow cytometry and staining. Culture of UC LPMCs with lyso-sulfatide glycolipid to determine sulfatide induction of epithelial cell cytotoxicity, IL-13 production and IL-13Rα2 expression. Blinded quantum dot-based phenotypic analysis to assess UC LPMC expression of IL-13Rα2, CD161 and IL-13.
  
  
  RESULTS
  Approximately 36% of UC LPMC were lyso-sulfatide tetramer positive, whereas few, if any, control LPMCs were positive. When tested, the positive cells were also CD3 and IL-13Rα2 positive. Culture of UC LPMC with lyso-sulfatide glycolipid showed that sulfatide stimulates UC LPMC production of IL-13 and induces UC CD161 LPMC-mediated cytotoxicity of activated epithelial cells; additionally, lyso-sulfatide induces enhanced expression of IL-13Rα2. Finally, blinded phenotypic analysis of UC LP MC using multicolour quantum dot-staining technology showed that approximately 60% of the LPMC bear both IL-13Rα2 and CD161 and most of these cells also produce IL-13.
  
  
  CONCLUSIONS
  These studies show that UC lamina propria is replete with Type II NKT cells responsive to lyso-sulfatide glycolipid and bearing IL-13Rα2. Since lyso-sulfatide is a self-antigen, these data suggest that an autoimmune response is involved in UC pathogenesis.
authors: Mucosal Immunity Section, Laboratory of Host Defenses, NIAID NIH, Bethesda, Maryland, USA.
authors: Ivan J
authors: IJ
authors: Fuss
authors: Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research FDA, Bethesda, Maryland, USA.
authors: Bharat
authors: B
authors: Joshi
authors: Mucosal Immunity Section, Laboratory of Host Defenses, NIAID NIH, Bethesda, Maryland, USA.
authors: Zhiqiong
authors: Z
authors: Yang
authors: Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research FDA, Bethesda, Maryland, USA.
authors: Heba
authors: H
authors: Degheidy
authors: Department of Surgery, University of Regensburg, Regensburg, Germany.
authors: Stefan
authors: S
authors: Fichtner-Feigl
authors: Department of Pathobiology, The Cleveland Clinic Foundation, Cleveland, Ohio, USA.
authors: Heitor
authors: H
authors: de Souza
authors: Department of Pathobiology, The Cleveland Clinic Foundation, Cleveland, Ohio, USA.
authors: Florian
authors: F
authors: Rieder
authors: Department of Pathobiology, The Cleveland Clinic Foundation, Cleveland, Ohio, USA.
authors: Franco
authors: F
authors: Scaldaferri
authors: Department of Pathobiology, The Cleveland Clinic Foundation, Cleveland, Ohio, USA.
authors: Anja
authors: A
authors: Schirbel
authors: Department of Pathobiology, The Cleveland Clinic Foundation, Cleveland, Ohio, USA.
authors: Melania
authors: M
authors: Scarpa
authors: Department of Pathobiology, The Cleveland Clinic Foundation, Cleveland, Ohio, USA.
authors: Gail
authors: G
authors: West
authors: Mucosal Immunity Section, Laboratory of Host Defenses, NIAID NIH, Bethesda, Maryland, USA.
authors: Chuli
authors: C
authors: Yi
authors: Mucosal Immunity Section, Laboratory of Host Defenses, NIAID NIH, Bethesda, Maryland, USA.
authors: Lili
authors: L
authors: Xu
authors: Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research FDA, Bethesda, Maryland, USA.
authors: Pamela
authors: P
authors: Leland
authors: Mucosal Immunity Section, Laboratory of Host Defenses, NIAID NIH, Bethesda, Maryland, USA.
authors: Michael
authors: M
authors: Yao
authors: Mucosal Immunity Section, Laboratory of Host Defenses, NIAID NIH, Bethesda, Maryland, USA.
authors: Peter
authors: P
authors: Mannon
authors: Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research FDA, Bethesda, Maryland, USA.
authors: Raj K
authors: RK
authors: Puri
authors: Department of Pathobiology, The Cleveland Clinic Foundation, Cleveland, Ohio, USA.
authors: Claudio
authors: C
authors: Fiocchi
authors: Mucosal Immunity Section, Laboratory of Host Defenses, NIAID NIH, Bethesda, Maryland, USA.
authors: Warren
authors: W
authors: Strober
mesh_terms: D001324:Autoantigens / Q000276:immunology*; D003093:Colitis, Ulcerative / Q000276:immunology*; D006017:Glycolipids; D006801:Humans; D066298:In Vitro Techniques; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology*; D055611:Natural Killer T-Cells / Q000276:immunology*; D011609:Psychosine / Q000031:analogs & derivatives / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D001324:Autoantigens; D006017:Glycolipids; D053663:Interleukin-13 Receptor alpha2 Subunit; D011609:Psychosine; C019064:psychosine-3'-sulfate ester
keywords: Cytokines; Inflammatory Bowel Disease; Intestinal T Cells; Ulcerative Colitis