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Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells

Nature Immunology volume 6, pages 507–514 (2005)Cite this article

A Corrigendum to this article was published on 17 February 2015

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Abstract

The control of damaging inflammation by the mucosal immune system in response to commensal and harmful ingested bacteria is unknown. Here we show epithelial cells conditioned mucosal dendritic cells through the constitutive release of thymic stromal lymphopoietin and other mediators, resulting in the induction of 'noninflammatory' dendritic cells. Epithelial cell–conditioned dendritic cells released interleukins 10 and 6 but not interleukin 12, and they promoted the polarization of T cells toward a 'classical' noninflammatory T helper type 2 response, even after exposure to a T helper type 1–inducing pathogen. This control of immune responses seemed to be lost in patients with Crohn disease. Thus, the intimate interplay between intestinal epithelial cells and dendritic cells may help to maintain gut immune homeostasis.

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Figure 1: Primary human gut DCs are unable to release IL-12 and promote TH2 cells in response to S. typhimurium.
Figure 2: EC supernatants do not induce DC maturation but instead condition TH2-promoting DCs.
Figure 3: TSLP is constitutively expressed by Caco-2 cells and is able to confer TH2-inducing ability.
Figure 4: Caco-2-conditioned DCs release IL-6 constitutively but lose the ability to release IL-12 in response to bacteria and to drive TH1 cell polarization by a TSLP-mediated mechanism.
Figure 5: Unconditioned DCs drive TH1 responses, whereas Caco-2-conditioned DCs induce typical TH2 cells.
Figure 6: Bacteria upregulate TSLP expression, but 'rescue' of the CL2 phenotype occurs only within a narrow window of TSLP concentration.
Figure 7: TSLP is constitutively expressed by isolated primary ECs of healthy but not diseased tissue.

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Change history

  • 20 November 2014

    In the version of this article initially published, the plots at top and middle left in Figure 5a were incorrect. The correct plots are now presented. The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank S. Chiocca and J.P. Kraehenbühl for critical reading of the manuscript; P. Larghi for continuous experimental help; E. Colli and F. Dalla Valle for technical assistance; and E. Torchiana from Miltenyi Biotech for technical support. Supported by Fondazione Italiana per la Ricerca sul Cancro (M.C.) and the Crohn's and Colitis Foundation of America and Associazione Italiana per la Ricerca sul Cancro, Italy.

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Author notes

  1. Marcello Chieppa

    Present address: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, USA

Authors and Affiliations

  1. Department of Experimental Oncology, European Institute of Oncology, Milan, I-20141, Italy

    Monica Rimoldi, Valentina Salucci, Francesca Avogadri & Maria Rescigno

  2. Department of Immunology, Istituto di Ricerche Farmacologiche 'Mario Negri', Milan, 20157, Italy

    Marcello Chieppa & Paola Allavena

  3. Department of Pathology and Laboratory Medicine, European Institute of Oncology, Milan, I-20141, Italy

    Angelica Sonzogni & Giuseppe Viale

  4. Division of General Surgery, University of Milan and Luigi Sacco Hospital, Milan, 20157, Italy

    Gianluca M Sampietro

  5. University of Milano-Bicocca and San Gerardo Hospital, Monza, 20052, Milan, Italy

    Angelo Nespoli

  6. University of Milan School of Medicine, Milan, 20141, Italy

    Giuseppe Viale

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Supplementary information

Supplementary Fig. 1

MoDCs conditioned with Caco-2 supernatant show similar response to bacteria in terms of changes in morphology and surface markers. (PDF 1527 kb)

Supplementary Fig. 2

Naive T cells stimulated with conditioned MoDCs proliferate similarly, regardless of treatment. (PDF 188 kb)

Supplementary Fig. 3

Naive T cells stimulated with conditioned MoDCs proliferate similarly, regardless of treatment. (PDF 187 kb)

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Rimoldi, M., Chieppa, M., Salucci, V. et al. Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells. Nat Immunol 6, 507–514 (2005). https://doi.org/10.1038/ni1192

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