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Goblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestine

Goblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestine

Nature volume 483, pages 345–349 (2012)Cite this article

Abstract

The intestinal immune system is exposed to a mixture of foreign antigens from diet, commensal flora and potential pathogens. Understanding how pathogen-specific immunity is elicited while avoiding inappropriate responses to the background of innocuous antigens is essential for understanding and treating intestinal infections and inflammatory diseases. The ingestion of protein antigen can induce oral tolerance, which is mediated in part by a subset of intestinal dendritic cells (DCs) that promote the development of regulatory T cells1. The lamina propria (LP) underlies the expansive single-cell absorptive villous epithelium and contains a large population of DCs (CD11c+ CD11b+ MHCII+ cells) comprised of two predominant subsets: CD103+ CX3CR1− DCs, which promote IgA production, imprint gut homing on lymphocytes and induce the development of regulatory T cells2,3,4,5,6,7,8,9, and CD103− CX3CR1+ DCs (with features of macrophages), which promote tumour necrosis factor-α (TNF-α) production, colitis, and the development of TH17 T cells5,6,7,10. However, the mechanisms by which different intestinal LP-DC subsets capture luminal antigens in vivo remains largely unexplored. Using a minimally disruptive in vivo imaging approach we show that in the steady state, small intestine goblet cells (GCs) function as passages delivering low molecular weight soluble antigens from the intestinal lumen to underlying CD103+ LP-DCs. The preferential delivery of antigens to DCs with tolerogenic properties implies a key role for this GC function in intestinal immune homeostasis.

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Acknowledgements

This work was supported in part by grants DK064798 (R.D.N.), AI083538 (R.D.N.), AI095550 (R.D.N. and M.J.M.), DK085941 (L.W.W.) and AI077600 (M.J.M.). The authors thank W. Beatty for assistance with confocal microscopy, C. Eagon for assistance with human specimens, the Alvin J. Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis for the use of the Siteman Flow Cytometry Core, which provided high-speed flow sorting and the Washington University Digestive Disease Research Core Center (DDRCC), which provided gnotobiotic mice. The Siteman Cancer Center is supported in part by an NCI Cancer Center Support Grant number P30 CA91842. The Washington University DDRCC is supported by grant P30-DK52574.

Author information Author notes

  1. Jeremiah R. McDole and Leroy W. Wheeler: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology and Immunology, Washington University School of Medicine, St Louis, 63110, Missouri, USA

    Jeremiah R. McDole, Baomei Wang & Mark J. Miller

  2. Department of Internal Medicine, Washington University School of Medicine, St Louis, 63110, Missouri, USA

    Leroy W. Wheeler, Keely G. McDonald, Kathryn A. Knoop & Rodney D. Newberry

  3. Department of Microbiology, Southern Illinois University, Carbondale, 62901, Illinois, USA

    Vjollca Konjufca

Authors
  1. Jeremiah R. McDole
  2. Leroy W. Wheeler
  3. Keely G. McDonald
  4. Baomei Wang
  5. Vjollca Konjufca
  6. Kathryn A. Knoop
  7. Rodney D. Newberry
  8. Mark J. Miller
Contributions

J.R.M. and L.W.W. contributed equally to this work. J.R.M., B.W. and V.K. performed two-photon imaging experiments and data analysis, L.W.W., K.A.K. and K.G.M. performed cell isolation, in vitro studies and immunofluorescence and data analysis, R.D.N. and M.J.M. conceived of the study, directed the experimental design, analysed the data and wrote the manuscript. R.D.N. and M.J.M. contributed equally to this work and are equal corresponding authors. All authors reviewed and discussed the manuscript.

Corresponding authors

Correspondence to Rodney D. Newberry or Mark J. Miller.

Ethics declarations Competing interests

The authors declare no competing financial interests.

Supplementary information About this article Cite this article

McDole, J., Wheeler, L., McDonald, K. et al. Goblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestine. Nature 483, 345–349 (2012). https://doi.org/10.1038/nature10863

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This article is cited by Editorial Summary Striking an immunological balance in the small intestine

How the balance between tolerance and immunity is maintained is an important question in immunology, and is of particular relevance to the small intestine, where innocuous antigens from the diet and potential pathogens are encountered simultaneously. McDole et al. show that goblet cells in the epithelium of the small intestine act as conduits through which small luminal antigens can be delivered to tolerance-inducing dendritic cells in the lamina propria, a layer of connective tissue beneath the epithelium. Through this mechanism, goblet cells could play a key part in promoting intestinal immune homeostasis.

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