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β8 Integrin Expression and Activation of TGF-β by Intestinal Dendritic Cells Are Determined by Both Tissue Microenvironment and Cell Lineage

Research output: Contribution to journalArticle

  • Mathilde Boucard-Jourdin
  • David Kugler
  • Marie-Laure Endale Ahanda
  • Sébastien This
  • Jaime De Calisto
  • Ailiang Zhang
  • J Rodrigo Mora
  • Lynda M Stuart
  • John Savill
  • Adam Lacy-Hulbert
  • Helena Paidassi

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Original languageEnglish
Pages (from-to)1968-1978
JournalJournal of Immunology
Volume197
Issue number5
Early online date1 Aug 2016
DOIs
Publication statusPublished - Sep 2017

Abstract

Activation of TGF-β by dendritic cells (DCs) expressing αvβ8 integrin is essential for the generation of intestinal regulatory T cells (Tregs) that in turn promote tolerance to intestinal Ags. We have recently shown that αvβ8 integrin is preferentially expressed by CD103(+) DCs and confers their ability to activate TGF-β and generate Tregs. However, how these DCs become specialized for this vital function is unknown. In this study, we show that β8 expression is controlled by a combination of factors that include DC lineage and signals derived from the tissue microenvironment and microbiota. Specifically, our data demonstrate that TGF-β itself, along with retinoic acid and TLR signaling, drives expression of αvβ8 in DCs. However, these signals only result in high levels of β8 expression in cells of the cDC1 lineage, CD8α(+), or CD103(+)CD11b(-) DCs, and this is associated with epigenetic changes in the Itgb8 locus. Together, these data provide a key illustrative example of how microenvironmental factors and cell lineage drive the generation of regulatory αvβ8-expressing DCs specialized for activation of TGF-β to facilitate Treg generation.

ID: 27582437