?8 Integrin Expression and Activation of TGF-? by Intestinal Dendritic Cells Are Determined by Both Tissue Microenvironment and Cell Lineage.

ABSTRACT: Activation of TGF-? by dendritic cells (DCs) expressing ?v?8 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 ?v?8 integrin is preferentially expressed by CD103(+) DCs and confers their ability to activate TGF-? and generate Tregs. However, how these DCs become specialized for this vital function is unknown. In this study, we show that ?8 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-? itself, along with retinoic acid and TLR signaling, drives expression of ?v?8 in DCs. However, these signals only result in high levels of ?8 expression in cells of the cDC1 lineage, CD8?(+), 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 ?v?8-expressing DCs specialized for activation of TGF-? to facilitate Treg generation.

SUBMITTER: Boucard-Jourdin M 

PROVIDER: S-EPMC4992650 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature