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.
Arribas-Rodríguez et al. (Sun,) studied this question.