*Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan; †Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Japan; ‡Laboratory of Mucosal Immunology, WPI Immunology Frontier Research Center, Osaka University, Suita, Japan; §Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Chiyoda, Japan; ‖Department of Molecular Pathology, Division of Health Sciences, Graduate School of Medicine and Health Science, Osaka University, Suita, Japan; ¶Department of Inflammatory Bowel Disease, Hyogo College of Medicine, Nishinomiya, Japan; and **Department of Therapeutics for Inflammatory Bowel Diseases, Graduate School of Medicine, Osaka University, Suita, Japan.
Inflamm Bowel Dis. 2017 Sep;23(9):1524-1534. doi: 10.1097/MIB.0000000000001204.
Human intestinal innate myeloid cells can be divided into 3 subsets: HLA-DRCD14 cells, HLA-DRCD103 dendritic cells (DCs), and HLA-DRCD14CD103 cells. CD103 DCs generate Treg cells and Th17 cells in the ileum, but their function in the colon remains largely unknown. This study characterized CD103 DCs in the colon and investigated whether these cells are implicated in the pathogenesis of ulcerative colitis (UC).
Normal intestinal mucosa was obtained from intact sites of patients with colorectal cancer (n = 24). Noninflamed and inflamed colonic tissues were obtained from surgically resected specimens of patients with UC (n = 13). Among LinCD45HLA-DR intestinal lamina propria cells, CD14 cells and CD103 DCs were sorted and analyzed for microRNA expression of cytokines and toll-like receptors by quantitative real-time polymerase chain reaction. In addition, IL-4/IL-5/IL-13/IL-17/IFN-γ production and Foxp3 expression by naive T cells cultured with CD14 cells and CD103 DCs were analyzed.
CD103 DCs in the normal colon showed lower expression of toll-like receptors and proinflammatory cytokines than CD14 cells. Coculture with naive T cells revealed that CD103 DCs generated Treg cells. CD103 DCs from patients with UC did not generate Treg cells, but they induced IFN-γ-, IL-13-, and IL-17-producing CD4 T cells and showed higher expression of IL6 (P < 0.0001), IL23A (P < 0.05), IL12p35 (P < 0.05), and TNF (P < 0.05).
In patients with UC, CD103 DCs show the impaired ability to generate Treg cells, but exhibit a colitogenic function inducing Th1/Th2/Th17 responses. These findings show how human CD103 DCs could contribute to the pathogenesis of UC.
人类肠道固有髓样细胞可分为 3 个亚群：HLA-DR+CD14+细胞、HLA-DR+CD103 树突状细胞（DC）和 HLA-DR+CD14+CD103 细胞。CD103 DC 在回肠中产生 Treg 细胞和 Th17 细胞，但它们在结肠中的功能仍知之甚少。本研究对结肠中的 CD103 DC 进行了特征描述，并探讨了这些细胞是否与溃疡性结肠炎（UC）的发病机制有关。
从大肠癌患者的完整部位获得正常肠道黏膜（n=24）。从接受手术切除的 UC 患者的非炎症和炎症结肠组织中获得非炎症和炎症结肠组织（n=13）。在 Lin-CD45+HLA-DR 肠道固有层细胞中，对 CD14 细胞和 CD103 DC 进行分选，并通过实时定量聚合酶链反应分析细胞因子和 Toll 样受体的 microRNA 表达。此外，分析了与 CD14 细胞和 CD103 DC 共培养的幼稚 T 细胞产生的 IL-4/IL-5/IL-13/IL-17/IFN-γ和 Foxp3 表达。
正常结肠中的 CD103 DC 表达的 Toll 样受体和促炎细胞因子低于 CD14 细胞。与幼稚 T 细胞共培养显示 CD103 DC 可产生 Treg 细胞。UC 患者的 CD103 DC 不能产生 Treg 细胞，但可诱导 IFN-γ+、IL-13+和 IL-17+产生 CD4+T 细胞，并表现出更高的 IL6（P＜0.0001）、IL23A（P＜0.05）、IL12p35（P＜0.05）和 TNF（P＜0.05）表达。
在 UC 患者中，CD103 DC 产生 Treg 细胞的能力受损，但具有诱导 Th1/Th2/Th17 反应的致结肠炎功能。这些发现表明人类 CD103 DC 如何有助于 UC 的发病机制。
