title: Enterocyte dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin expression in inflammatory bowel disease.
abstract: OBJECTIVE
  To investigate dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) expression in intestinal epithelial cells (IECs) in inflammatory bowel disease (IBD).
  
  
  METHODS
  The expression of DC-SIGN in IECs was examined by immunohistochemistry of intestinal mucosal biopsies from 32 patients with IBD and 10 controls. Disease activity indices and histopathology scores were used to assess the tissue lesions and pathologic damage. Animal studies utilized BALB/c mice with dextran sodium sulfate (DSS)-induced colitis treated with anti-P-selectin lectin-EGF domain monoclonal antibody (PsL-EGFmAb). Controls, untreated and treated mice were sacrificed after 7 d, followed by isolation of colon tissue and IECs. Colonic expression of DC-SIGN, CD80, CD86 and MHC II was examined by immunohistochemistry or flow cytometry. The capacity of mouse enterocytes or dendritic cells to activate T cells was determined by co-culture with naïve CD4(+) T cells. Culture supernatant and intracellular levels of interleukin (IL)-4 and interferon (IFN)-γ were measured by enzyme-linked immunosorbent assay and flow cytometry, respectively. The ability of IECs to promote T cell proliferation was detected by flow cytometry staining with carboxyfluorescein diacetate succinimidyl ester.
  
  
  RESULTS
  Compared with controls, DC-SIGN expression was significantly increased in IECs from patients with Crohn's disease (P < 0.01) or ulcerative colitis (P < 0.05). DC-SIGN expression was strongly correlated with disease severity in IBD (r = 0.48; P < 0.05). Similarly, in the DSS-induced colitis mouse model, IECs showed upregulated expression of DC-SIGN, CD80, CD86 and MHC, and DC-SIGN expression was positively correlated with disease activity (r = 0.62: P < 0.01). IECs from mouse colitis stimulated naïve T cells to generate IL-4 (P < 0.05). Otherwise, dendritic cells promoted a T-helper-1-skewing phenotype by stimulating IFN-γ secretion. However, DC-SIGN expression and T cell differentiation were suppressed following treatment of mice with DSS-induced colitis with PsL-EGFmAb. The proliferation cycles of CD4(+) T cells from mice with DSS-induced colitis appeared as five cycles, which was more than in the control and treated groups. These results suggest that IECs can promote T cell proliferation.
  
  
  CONCLUSIONS
  IECs regulate tissue-associated immune compartments under the control of DC-SIGN in IBD.
authors.affiliation: Jing-Qing Zeng, Chun-Di Xu, Tong Zhou, Jing Wu, Kai Lin, Wei Liu, Xin-Qiong Wang, Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Jing-Qing
authors.initials: JQ
authors.lastname: Zeng
authors.affiliation: Jing-Qing Zeng, Chun-Di Xu, Tong Zhou, Jing Wu, Kai Lin, Wei Liu, Xin-Qiong Wang, Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Chun-Di
authors.initials: CD
authors.lastname: Xu
authors.affiliation: Jing-Qing Zeng, Chun-Di Xu, Tong Zhou, Jing Wu, Kai Lin, Wei Liu, Xin-Qiong Wang, Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Jing-Qing Zeng, Chun-Di Xu, Tong Zhou, Jing Wu, Kai Lin, Wei Liu, Xin-Qiong Wang, Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Jing-Qing Zeng, Chun-Di Xu, Tong Zhou, Jing Wu, Kai Lin, Wei Liu, Xin-Qiong Wang, Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Lin
authors.affiliation: Jing-Qing Zeng, Chun-Di Xu, Tong Zhou, Jing Wu, Kai Lin, Wei Liu, Xin-Qiong Wang, Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Jing-Qing Zeng, Chun-Di Xu, Tong Zhou, Jing Wu, Kai Lin, Wei Liu, Xin-Qiong Wang, Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Xin-Qiong
authors.initials: XQ
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D018920:Coculture Techniques; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003093:Colitis, Ulcerative / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003424:Crohn Disease / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D020895:Enterocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D008807:Mice, Inbred BALB C; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D016264:Dextran Sulfate; D018836:Inflammation Mediators; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
keywords: Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin; Dendritic cells; Immune compartmentalization; Inflammatory bowel disease; Intestinal epithelial cells