Type 1 and CD103+ Type 2 Conventional Dendritic Cells Are Decreased in Active Patients with Ulcerative Colitis but Not with Crohn's Disease

Abstract

This study aimed to characterize human intestinal conventional dendritic cells (cDCs) in health and inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD). Three cDC subsets (CD103− cDC2, CD103+ cDC2, and cDC1) were identified from lamina propria mononuclear cells. Their phenotype and function were analyzed in healthy and IBD-inflamed gut tissues. In the healthy gut, cDC2 predominated over cDC1, with CD103+ cDC2 dominating the duodenum and CD103− cDC2 prevalent in the ileum and colon. CD103+ cDC2 expressed higher PD-L1 and produced more IL-10. In culture, CD103+ cDC2 increased proportionally unless inhibited by LPS. All subsets induced IL-10+ helper T-cell differentiation, with ileal cDCs being more stimulatory than colonic ones. In IBD, cDCs showed constitutively lower SIRPα expression across conditions. Notably, UC-inflamed colon exhibited reduced cDC1 and CD103+ cDC2, while CD-inflamed colon maintained these subsets but showed increased T-cell stimulation and IL-17+ T-cell priming. Intestinal cDC subsets prime IL-10+ helper T-cells in health. In UC, reduced cDC1 and CD103+ cDC2 in inflamed mucosa contrast with CD, suggesting distinct pathogenic mechanisms that could inform targeted therapies.