CD103+ Dendritic Cell Function Is Altered in the Colons of Patients with Ulcerative Colitis

Hiroshi Matsuno, Hisako Kayama, Junichi Nishimura, Yuki Sekido, Hideki Osawa, Soumik Barman, Takayuki Ogino, Hidekazu Takahashi, Naotsugu Haraguchi, Taishi Hata, Chu Matsuda, Hirofumi Yamamoto, Motoi Uchino, Hiroki Ikeuchi, Yuichiro Doki, Masaki Mori, Kiyoshi Takeda, Tsunekazu Mizushima

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1524-1534
Number of pages11
JournalInflammatory bowel diseases
Volume23
Issue number9
DOIs
Publication statusPublished - Sep 1 2017
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Gastroenterology

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    Matsuno, H., Kayama, H., Nishimura, J., Sekido, Y., Osawa, H., Barman, S., Ogino, T., Takahashi, H., Haraguchi, N., Hata, T., Matsuda, C., Yamamoto, H., Uchino, M., Ikeuchi, H., Doki, Y., Mori, M., Takeda, K., & Mizushima, T. (2017). CD103+ Dendritic Cell Function Is Altered in the Colons of Patients with Ulcerative Colitis. Inflammatory bowel diseases, 23(9), 1524-1534. https://doi.org/10.1097/MIB.0000000000001204