Thetis cells induce food-specific Treg cell differentiation and oral tolerance

作者：Yollanda Edwirges Moreira Franco, Vanja Cabric, Tyler Park, Blossom Akagbosu, Zihan Zhao, Yun Lo, Logan Fisher, Gayathri Shibu, Yoselin A. Paucar Iza, Christina C. Leslie, Chrysothemis C. Brown · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2024 · DOI：10.1101/2024.05.08.592952 · 被引用次数：12 · 研究领域：Food Allergy and Anaphylaxis Research、IL-33, ST2, and ILC Pathways、Immune Cell Function and Interaction

Abstract The intestinal immune system must establish tolerance to food antigens to prevent onset of allergic and inflammatory diseases. Peripherally generated regulatory T (pTreg) cells play an essential role in suppressing inflammatory responses to allergens; however, the antigen-presenting cell (APC) that instructs food-specific pTreg cells is not known. Here, we show that antigen presentation and TGF-β activation by a subset of RORγt + antigen-presenting cells (APC), Thetis cells IV (TC IV), is required for food-induced pTreg cell differentiation and oral tolerance. By contrast, antigen presentation by dendritic cells (DCs) was dispensable for pTreg induction but required for T H 1 effector responses, highlighting a division of labor between tolerogenic TCs and pro-inflammatory DCs. While antigen presentation by TCs was required for food-specific pTreg generation both in early life and adulthood, the increased abundance of TCs in the peri-weaning period was associated with a window of opportunity for enhanced pTreg differentiation. These findings establish a critical role for TCs in oral tolerance and suggest that these cells may represent a key therapeutic target for the treatment of food-associated allergic and inflammatory diseases.