A breakthrough study utilizing conditional gene deletion and single-cell transcriptomics has identified a unique subset of antigen-presenting cells (APCs) characterized by high expression of PRDM16 and RORγt. These newly termed tolerogenic dendritic cells (tolDCs) exhibit a distinct gene expression and chromatin profile compared to conventional dendritic cells (cDCs) and innate lymphoid cells type 3 (ILC3s). Mice deficient in PRDM16 or RORγt within CD11c+ cells showed impaired development of microbiota- and food antigen-specific regulatory T cells (pTregs), leading to heightened Th17 and Th2 responses and signs of type 2 intestinal inflammation.Understanding the role of these rare tolDCs in regulating immune tolerance towards food and gut microbiota could pave the way for novel therapeutic interventions targeting immune dysregulation and inflammatory conditions. The findings underscore the intricate interplay between specific cell subsets and immune responses, offering potential insights for personalized medicine approaches in treating autoimmune diseases or allergies. Further research exploring the mechanisms underlying tolDC function and their interactions within the gut environment may unlock new avenues for precision medicine strategies aimed at modulating immune tolerance and preventing inflammatory disorders.
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