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Annual Review of Immunology

Volume 43, 2025

Antigen Uptake in the Gut: An Underappreciated Piece to the Puzzle?

  • Devesha H. Kulkarni1 and Rodney D. Newberry2
  • 1Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA 2John T. Milliken Department of Medicine, School of Medicine, Washington University, Saint Louis, Missouri, USA; email: [email protected]
  • Vol. 43:571-588 (Volume publication date April 2025)
  • Copyright © 2025 by the author(s).
    This work is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See credit lines of images or other third-party material in this article for license information.

Abstract

The mammalian gut is a vast, diverse, and dynamic single-layer epithelial surface exposed to trillions of microbes, microbial products, and the diet. Underlying this epithelium lies the largest collection of immune cells in the body; these cells encounter luminal substances to generate antigen-specific immune responses characterized by tolerance at homeostasis and inflammation during enteric infections. How the outcomes of antigen-specific tolerance and inflammation are appropriately balanced is a central question in mucosal immunology. Furthermore, how substances large enough to generate antigen-specific responses cross the epithelium and encounter the immune system in homeostasis and during inflammation remains largely unexplored. Here we discuss the challenges presented to the gut immune system, the identified pathways by which luminal substances cross the epithelium, and insights suggesting that the pathways used by substances to cross the epithelium affect the ensuing immune response.

Keyword(s): antigen, goblet cell, intestine, microfold cell, paracellular transport, transepithelial dendrite
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2025-04-25
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Antigen Uptake in the Gut: An Underappreciated Piece to the Puzzle?
Annual Review of Immunology 43, 571 (2025); https://doi.org/10.1146/annurev-immunol-082523-090154
/content/journals/10.1146/annurev-immunol-082523-090154
/content/journals/10.1146/annurev-immunol-082523-090154
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