CD103+ Dendritic Cell Function Is Altered in the Colons of Patients with Ulcerative Colitis. Issue 9 (11th July 2017)

• Record Type: Journal Article
• Authors: Matsuno, Hiroshi; Kayama, Hisako; Nishimura, Junichi; Sekido, Yuki; Osawa, Hideki; Barman, Soumik; Ogino, Takayuki; Takahashi, Hidekazu; Haraguchi, Naotsugu; Hata, Taishi; Matsuda, Chu; Yamamoto, Hirofumi; Uchino, Motoi; Ikeuchi, Hiroki; Doki, Yuichiro; Mori, Masaki; Takeda, Kiyoshi; Mizushima, Tsunekazu
• Is Part Of: Inflammatory bowel diseases. Volume 23:Issue 9(2017)
• Page Start: 1524
• Page End: 1534
• Publication Date: 2017-07-11
• Subjects: ulcerative colitis -- human large intestinal lamina propria -- CD103+ dendritic cell -- Foxp3+ regulatory T cells; Inflammatory bowel diseases -- Periodicals; Colitis, Ulcerative -- Periodicals; Crohn Disease -- Periodicals; Inflammatory Bowel Diseases -- Periodicals; 616.344
• DOI: 10.1097/MIB.0000000000001204
• Languages: English
• ISSNs: 1078-0998

Abstract

Abstract : 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-DR high 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. 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-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). 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.