Letter | Published:

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

Nature volume 483, pages 345349 (15 March 2012) | Download Citation

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

    • Jeremiah R. McDole
    •  & Leroy W. Wheeler

    These authors contributed equally to this work.

Affiliations

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

    • Jeremiah R. McDole
    • , Baomei Wang
    •  & Mark J. Miller
  2. Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA

    • Leroy W. Wheeler
    • , Keely G. McDonald
    • , Kathryn A. Knoop
    •  & Rodney D. Newberry
  3. Department of Microbiology, Southern Illinois University, Carbondale, Illinois 62901, USA

    • Vjollca Konjufca

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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.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

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

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    This file contains Supplementary Figures 1-9 and Supplementary Legends for Supplementary Movies 1-6.

Videos

  1. 1.

    Supplementary Movie 1

    This montaged movie shows a montage of 4 movies.

  2. 2.

    Supplementary Movie 2

    This cecal patch with GAP movie shows a cecal patch with a GAP.

  3. 3.

    Supplementary Movie 3

    This GAP with nucleus movie shows a GAP filling.

  4. 4.

    Supplementary Movie 4

    This movie demonstrates paracellular leak and a 3D reconstruction of a confocal image.

  5. 5.

    Supplementary Movie 5

    This montaged movie shows a montage of 4 movies.

  6. 6.

    Supplementary Movie 6

    This movie demonstrates luminal Ova being delivered to a LP-DC via a GAP.

About this article

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DOI

https://doi.org/10.1038/nature10863

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