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

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.