Intestinal epithelial cells promote colitis-protective regulatory T-cell differentiation through dendritic cell conditioning

I. D. Iliev, E. Mileti, G. Matteoli, M. Chieppa, Maria Rescigno

Research output: Contribution to journalArticle

Abstract

Intestinal dendritic cells (DCs) have been shown to display specialized functions, including the ability to promote gut tropism to lymphocytes, to polarize noninflammatory responses, and to drive the differentiation of adaptive Foxp3+ regulatory T (Treg) cells. However, very little is known about what drives the mucosal phenotype of DCs. Here, we present evidence that the local microenvironment, and in particular intestinal epithelial cells (ECs), drive the differentiation of Treg-cell-promoting DCs, which counteracts Th1 and Th17 development. EC-derived transforming growth factor-β (TGF-β) and retinoic acid (RA), but not thymic stromal lymphopoietin (TSLP), were found to be required for DC conversion. After EC contact, DCs upregulated CD103 and acquired a tolerogenic phenotype. EC-conditioned DCs were capable of inducing de novo Treg cells with gut-homing properties that when adoptively transferred, protected mice from experimental colitis. Thus, we have uncovered an essential mechanism in which EC control of DC function is required for tolerance induction.

Original languageEnglish
Pages (from-to)340-350
Number of pages11
JournalMucosal Immunology
Volume2
Issue number4
DOIs
Publication statusPublished - 2009

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ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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