High Fat and Sugar Diet Increases Enteric cDC1 and Oral Antigen‐Specific Tregs

Diet-induced obesity is a growing global health concern linked to various immunological alterations. Dendritic cells (DCs) are major regulators of the balance between pro-inflammatory and tolerogenic immune responses. Conventional Type 1 DCs (cDC1) contribute to oral tolerance by affecting the generation of food specific regulatory T cells (Tregs). Nevertheless, whether obesity affects cDC1/Treg pathways and the generation of food tolerance remains poorly understood. Here, we investigated the spatio-temporal impact of a high-fat, high-sugar diet (HFHSD) on the enteric immune system. Enteric immune composition was primarily altered by diet and intestinal region, independently of the duration of the dietary regimen. Notably, the lamina propria of animals fed with high-caloric diet was enriched in cDC1 overtime. While diet did neither reprogramme cDC1 gut-homing markers, nor costimulatory molecules nor cytokines, it increased intestinal cDC1 levels, which correlated with increased Tregs during oral tolerance protocols. Our findings contribute to a better understanding of high-caloric diet and food intolerances, while revealing a remarkable plasticity of the intestinal immune system in response to diet.