CD103+ Dendritic Cell Function Is Altered in the Colons of Patients with Ulcerative Colitis
CD103+ Dendritic Cell Function Is Altered in the Colons of Patients with Ulcerative Colitis
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DOI：
10.1097/mib.0000000000001204
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发表时间：
2017-09-01
影响因子：
4.9
通讯作者：
Mizushima, Tsunekazu
中科院分区：
文献类型：
--
作者：
Matsuno, Hiroshi;Kayama, Hisako;Mizushima, Tsunekazu
背景资料：人肠道先天性髓系细胞可分为3个亚群：HLA-DR（high）CD 14（+）细胞、HLA-DR（high）CD 103（+）树突状细胞（DCs）和HLA-DR（high）CD 14（-）CD 103（-）细胞。CD 103（+）DC在回肠中产生Treg细胞和Th 17细胞，但它们在结肠中的功能在很大程度上仍然未知。本研究对结肠组织中的CD 103（+）DCs进行了鉴定，并探讨了这些细胞是否参与了溃疡性结肠炎（UC）的发病机制。从UC患者的手术切除标本中获得非炎症和炎症结肠组织（n = 13）。在Lin（-）CD 45（+）HLA-DR high肠固有层细胞中，分选CD 14（+）细胞和CD 103（+）DC，并通过定量实时聚合酶链反应分析细胞因子和toll样受体的microRNA表达。结果：正常结肠组织中CD 103（+）DCs较CD 14（+）DCs表达Toll样受体和促炎细胞因子，但CD 103（+）DCs表达Toll样受体和促炎细胞因子的能力较CD 14（+）DCs低。与初始T细胞共培养显示CD 103（+）DC产生Treg细胞。来自UC患者的CD 103 + DC不产生Treg细胞，但它们诱导产生IFN-γ、IL-13和IL-17的CD 4（+）T细胞，并显示出较高的IL 6表达（P < 0.0001），IL 23 A（P < 0.05），IL 12p35（P < 0.05），和TNF（P < 0.05）。结论：在UC患者中，CD 103（+）DC显示出产生Treg细胞的能力受损，但显示出诱导Th 1/Th 2/Th 17应答的大肠杆菌生成功能。这些发现显示了人CD 103（+）DCs如何参与UC的发病机制。
Background: Human intestinal innate myeloid cells can be divided into 3 subsets: HLA-DR(high)CD14(+) cells, HLA-DR(high)CD103(+) dendritic cells (DCs), and HLA-DR(high)CD14(-)CD103(-) 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).Methods: 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 Lin(-)CD45(+) HLA-DRhigh 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-gamma production and Foxp3 expression by naive T cells cultured with CD14(+) cells and CD103(+) DCs were analyzed.Results: 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-gamma-, 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).Conclusions: 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.