A coordinated cellular network regulates tolerance to food

Anna Rudnitsky, Hanna Oh, Maya Margolin, Bareket Dassa, Inbar Shteinberg, Liat Stoler-Barak, Ziv Shulman and Ranit Kedmi ()
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Anna Rudnitsky: Weizmann Institute of Science
Hanna Oh: Weizmann Institute of Science
Maya Margolin: Weizmann Institute of Science
Bareket Dassa: Weizmann Institute of Science
Inbar Shteinberg: Weizmann Institute of Science
Liat Stoler-Barak: Weizmann Institute of Science
Ziv Shulman: Weizmann Institute of Science
Ranit Kedmi: Weizmann Institute of Science

Nature, 2025, vol. 644, issue 8075, 231-240

Abstract: Abstract 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 RORγt antigen-presenting cells4–8 and not by conventional dendritic cells. Instead, our data suggest that pTreg cell–cDC1 interactions during homeostasis limit the expansion of food-specific CD8αβ T cells. This regulation is disrupted by infection or food poisoning, enabling dietary CD8αβ T cells to expand and acquire effector functions in response to mimicked food antigens. Unlike in typical infections, after the pathogen is cleared, dietary CD8αβ 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.

Date: 2025
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DOI: 10.1038/s41586-025-09173-x

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