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T cell fate is dictated by different antigen presenting cells in response to dietary versus gut epithelial self-antigen

Created on 09 Nov 2025

Authors

Zhou, Y. D., Brown, H., Schaffer, E., Taylor, G. M., Fiske, K. L., Komnick, M. R., Lopez, S., Dermody, T. S., Esterhazy, D.

Abstract

We investigated whether T cell responses and antigen-presenting cell (APC) requirements in gut-draining lymph nodes differ by antigen source, diet versus epithelium. Using mice fed ovalbumin (OVA) or expressing secreted (s), cytosolic (c), or transmembrane (tm) epithelial OVA, we compared OVA-specific T cell fates. At baseline and after reovirus infection, T cell responses were comparable across models. However, helminth infection induced Th2 cell polarization in sOVA and tmOVA but not cOVA or OVA-fed mice. BATF3 APCs were indispensable for CD4 T cell proliferation only in cOVA mice yet drove Treg cell differentiation across all epithelial OVA models. In contrast, antigen presentation by ROR{gamma}tMHC-II APCs was exclusively required for Treg cell induction by dietary OVA. These distinct APC dependencies correlated with susceptibility to pathology elicited by dietary versus epithelial self-antigens. Thus, antigen origin and presentation context are integrated to shape T cell fate, a new framework for predicting gut immune outcomes.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 09 Nov 2025.

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