Preferential Expression of Integrin αvβ8 Promotes Generation of Regulatory T Cells by Mouse CD103+ Dendritic Cells

Abstract

Immune responses in the intestine are controlled by regulatory T cells (Tregs), which prevent inflammation in response to commensal bacteria. A specific population of intestinal dendritic cells (DCs), marked by expression of CD103, generate Tregs more efficiently than other DC populations through mechanisms that involve retinoic acid and transforming growth factor (TGF)-β. However, it is not clear how CD103(+) DCs are specialized for this function. We investigated the ability of CD103(+) DCs to promote Treg generation through activation of TGF-β and the role of integrins with the αv subunit in this process. Naïve T cells were cultured with purified DCs from mesenteric lymph nodes (MLNs) or intestines of wild-type and αv conditional knockout mice to assess generation of Tregs. Antigens were administered orally to mice, and antigen-specific generation of Tregs was measured in intestinal tissues. Expression of the integrin αv subunit was measured in purified subpopulations of DCs by quantitative polymerase chain reaction and immunoblot analyses. In vitro, CD103(+) DCs generated more Tregs in the presence of latent TGF-β than other MLN DCs. Efficient generation of Tregs required expression of the integrin αv subunit by DCs; mice that lacked αv in immune cells did not convert naïve T cells to intestinal Tregs in response to oral antigen. CD103(+) DCs derived from the MLNs selectively expressed high levels of integrin αvβ8 compared with other populations of DCs. Expression of αvβ8 is required for CD103(+) DCs to become specialized and activate latent TGF-β and generate Tregs during the induction of tolerance to intestinal antigens in mice.