A coordinated cellular network regulates tolerance to food

• 成果类型: Article
• 署名作者: Rudnitsky, Anna; Oh, Hanna; Margolin, Maya; Dassa, Bareket; Shteinberg, Inbar; Stoler-Barak, Liat; Shulman, Ziv; Kedmi, Ranit
• 署名单位: Weizmann Institute of Science; Weizmann Institute of Science
• 刊物名称: Nature
• ISSN/ISSBN: 0028-3200
• DOI: 10.1038/s41586-025-09173-x
• 发表日期: 2025-08-07
• 关键词: classical dendritic cells; cd8(+) t-cells; oral tolerance; infection; memory; population; drives

摘要

To absorb nutrients and support commensal microorganisms, the host induces tolerogenic immune responses through peripheral regulatory T (pTreg) cells1,2. Previous studies identified conventional type 1 dendritic cells (cDC1s) as initiators of dietary pTreg cells3. However, here we report that food-specific pTreg cells are induced exclusively by the recently identified ROR gamma t antigen-presenting cells4, 5, 6, 7-8 and not by conventional dendritic cells. Instead, our data suggest that pTreg cell-cDC1 interactions during homeostasis limit the expansion of food-specific CD8 alpha beta T cells. This regulation is disrupted by infection or food poisoning, enabling dietary CD8 alpha beta T cells to expand and acquire effector functions in response to mimicked food antigens. Unlike in typical infections, after the pathogen is cleared, dietary CD8 alpha beta T cells do not expand in response to their corresponding dietary antigens. Thus, we propose that, in response to dietary antigens, tolerance is mediated by a circuit of dedicated antigen-presenting cells and T cells. When the host is challenged by infection, this circuit permits the transient expansion of protective effector responses without compromising the overall strategy of tolerance that ensures safe food consumption.