IL-13Rα2-bearing, type II NKT cells reactive to sulfatide self-antigen populate the mucosa of ulcerative colitis. Issue 11 (10th February 2014)

• Record Type: Journal Article
• Authors: Fuss, Ivan J; Joshi, Bharat; Yang, Zhiqiong; Degheidy, Heba; Fichtner-Feigl, Stefan; de Souza, Heitor; Rieder, Florian; Scaldaferri, Franco; Schirbel, Anja; Scarpa, Melania; West, Gail; Yi, Chuli; Xu, Lili; Leland, Pamela; Yao, Michael; Mannon, Peter; Puri, Raj K; Fiocchi, Claudio; Strober, Warren
• Is Part Of: Gut. Volume 63:Issue 11(2014)
• Page Start: 1728
• Page End: 1736
• Publication Date: 2014-02-10
• Subjects: Inflammatory Bowel Disease -- Cytokines -- Ulcerative Colitis -- Intestinal T Cells; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gutjnl-2013-305671
• Languages: English
• ISSNs: 0017-5749

Abstract

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. Design: 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.