| First Author | Boucard-Jourdin M | Year | 2016 |
| Journal | J Immunol | Volume | 197 |
| Issue | 5 | Pages | 1968-78 |
| PubMed ID | 27481847 | Mgi Jnum | J:317672 |
| Mgi Id | MGI:6844267 | Doi | 10.4049/jimmunol.1600244 |
| Citation | Boucard-Jourdin M, et al. (2016) beta8 Integrin Expression and Activation of TGF-beta by Intestinal Dendritic Cells Are Determined by Both Tissue Microenvironment and Cell Lineage. J Immunol 197(5):1968-78 |
| abstractText | Activation of TGF-beta by dendritic cells (DCs) expressing alphavbeta8 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 alphavbeta8 integrin is preferentially expressed by CD103(+) DCs and confers their ability to activate TGF-beta and generate Tregs. However, how these DCs become specialized for this vital function is unknown. In this study, we show that beta8 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-beta itself, along with retinoic acid and TLR signaling, drives expression of alphavbeta8 in DCs. However, these signals only result in high levels of beta8 expression in cells of the cDC1 lineage, CD8alpha(+), 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 alphavbeta8-expressing DCs specialized for activation of TGF-beta to facilitate Treg generation. |
