CD103+ Dendritic Cell Function Is Altered in the Colons of Patients with Ulcerative Colitis
Human intestinal innate myeloid cells can be divided into 3 subsets: HLA-DRhighCD14+ cells, HLA-DRhighCD103+ dendritic cells (DCs), and HLA-DRhighCD14−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-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.