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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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.
The authors declare no competing financial interests.
MoDCs conditioned with Caco-2 supernatant show similar response to bacteria in terms of changes in morphology and surface markers. (PDF 1527 kb)
Naive T cells stimulated with conditioned MoDCs proliferate similarly, regardless of treatment. (PDF 188 kb)
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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