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

A Corrigendum to this article was published on 17 February 2015

This article has been updated

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.

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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Correspondence to Maria Rescigno.

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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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