Zeng Jing-Qing, Xu Chun-Di, Zhou Tong, Wu Jing, Lin Kai, Liu Wei, Wang Xin-Qiong
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.
World J Gastroenterol. 2015 Jan 7;21(1):187-95. doi: 10.3748/wjg.v21.i1.187.
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).
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.
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.
IECs regulate tissue-associated immune compartments under the control of DC-SIGN in IBD.
研究炎症性肠病（IBD）中肠上皮细胞（IECs）树突状细胞特异性细胞间黏附分子3结合非整合素（DC-SIGN）的表达情况。
采用免疫组织化学法检测32例IBD患者和10例对照者肠黏膜活检标本中IECs的DC-SIGN表达。采用疾病活动指数和组织病理学评分评估组织损伤和病理损害。动物实验利用葡聚糖硫酸钠（DSS）诱导的BALB/c小鼠结肠炎模型，用抗P-选择素凝集素-表皮生长因子结构域单克隆抗体（PsL-EGFmAb）进行治疗。7 d后处死未治疗和治疗后的对照小鼠，分离结肠组织和IECs。通过免疫组织化学或流式细胞术检测结肠中DC-SIGN、CD80、CD86和MHC II的表达。通过与初始CD4(+) T细胞共培养来确定小鼠肠上皮细胞或树突状细胞激活T细胞的能力。分别采用酶联免疫吸附测定法和流式细胞术检测培养上清液和细胞内白细胞介素（IL）-4和干扰素（IFN）-γ水平。通过羧基荧光素二乙酸琥珀酰亚胺酯流式细胞术染色检测IECs促进T细胞增殖的能力。
与对照组相比，克罗恩病患者（P < 0.01）或溃疡性结肠炎患者（P < 0.05）的IECs中DC-SIGN表达显著增加。DC-SIGN表达与IBD疾病严重程度密切相关（r = 0.48；P < 0.05）。同样，在DSS诱导的结肠炎小鼠模型中，IECs的DC-SIGN、CD80、CD86和MHC表达上调，且DC-SIGN表达与疾病活动度呈正相关（r = 0.62：P < 0.01）。来自小鼠结肠炎的IECs刺激初始T细胞产生IL-4（P < 0.05）。此外，树突状细胞通过刺激IFN-γ分泌促进T辅助细胞1偏向性表型。然而，用PsL-EGFmAb治疗DSS诱导的结肠炎小鼠后，DC-SIGN表达和T细胞分化受到抑制。DSS诱导的结肠炎小鼠的CD4(+) T细胞增殖周期为5个周期，多于对照组和治疗组。这些结果表明IECs可促进T细胞增殖。
在IBD中，IECs在DC-SIGN的调控下调节组织相关免疫区室。
