Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2015; 21(1): 187-195
Published online Jan 7, 2015. doi: 10.3748/wjg.v21.i1.187
Enterocyte dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin expression in inflammatory bowel disease
Jing-Qing Zeng, Chun-Di Xu, Tong Zhou, Jing Wu, Kai Lin, Wei Liu, Xin-Qiong Wang
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
Jing-Qing Zeng, Department of Pediatrics, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
Author contributions: Xu CD and Zhou T designed the research; Zeng JQ, Lin K, Liu W and Wang XQ performed the research and analyzed the data; Zeng JQ and Wu J wrote the paper; all the authors have read and approved the final version to be published.
Supported by Grants from the National Natural Science Foundation of China No. 81000163, No. 81070567, and No. 81170363
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Chun-Di Xu, MD, Professor, Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Erlu, Shanghai 200025, China. chundixu55@163.com
Telephone: +86-21-64370045 Fax: +86-21-64333548
Received: May 23, 2014
Peer-review started: May 26, 2014
First decision: June 18, 2014
Revised: July 10, 2014
Accepted: July 24, 2014
Article in press: July 25, 2014
Published online: January 7, 2015
Processing time: 228 Days and 14.1 Hours
Abstract

AIM: 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.

CONCLUSION: IECs regulate tissue-associated immune compartments under the control of DC-SIGN in IBD.

Keywords: Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin; Dendritic cells; Immune compartmentalization; Inflammatory bowel disease; Intestinal epithelial cells

Core tip: Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) functions as an adhesion and antigen-presenting molecule. We found that DC-SIGN was expressed by intestinal epithelial cells, which induced differentiation and proliferation of T cells under the control of DC-SIGN.