Increased Th17-inducing activity of CD14+ CD163low myeloid cells in intestinal lamina propria of patients with Crohn's disease

Takayuki Ogino, Junichi Nishimura, Soumik Barman, Hisako Kayama, Satoshi Uematsu, Daisuke Okuzaki, Hideki Osawa, Naotsugu Haraguchi, Mamoru Uemura, Taishi Hata, Ichiro Takemasa, Tsunekazu Mizushima, Hirofumi Yamamoto, Kiyoshi Takeda, Yuichiro Doki, Masaki Mori

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71 Citations (Scopus)

Abstract

Background & Aims Abnormal activity of innate immune cells and T-helper (Th) 17 cells has been implicated in the pathogenesis of autoimmune and inflammatory diseases, including Crohn's disease (CD). Intestinal innate immune (myeloid) cells have been found to induce development of Th17 cells in mice, but it is not clear if this occurs in humans or in patients with CD. We investigated whether human intestinal lamina propria cells (LPCs) induce development of Th17 cells and whether these have a role in the pathogenesis of CD. Methods Normal intestinal mucosa samples were collected from patients with colorectal cancer and noninflamed and inflamed regions of mucosa were collected from patients with CD. LPCs were isolated by enzymatic digestion and analyzed for expression of HLA-DR, lineage markers CD14 and CD163 using flow cytometry. Results Among HLA-DRhigh Lin- cells, we identified a subset of CD14+ CD163low cells in intestinal LPCs; this subset expressed Toll-like receptor (TLR) 2, TLR4, and TLR5 mRNAs and produced interleukin (IL)-6, IL-1β, and tumor necrosis factor in response to lipopolysaccharide. In vitro co-culture with naïve T cells revealed that CD14+ CD163low cells induced development of Th17 cells. CD14+ CD163low cells from inflamed regions of mucosa of patients with CD expressed high levels of IL-6, IL-23p19, and tumor necrosis factor mRNAs, and strongly induced Th17 cells. CD14+ CD163 low cells from the noninflamed mucosa of patients with CD also had increased abilities to induce Th17 cells compared with those from normal intestinal mucosa. Conclusions CD14+ CD163low cells in intestinal LPCs from normal intestinal mucosa induce differentiation of naive T cells into Th17 cells; this activity is increased in mucosal samples from patients with CD. These findings show how intestinal myeloid cell types could contribute to pathogenesis of CD and possibly other Th17-associated diseases.

Original languageEnglish
Pages (from-to)1380-1391.e1
JournalGastroenterology
Volume145
Issue number6
DOIs
Publication statusPublished - Dec 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

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