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

BACKGROUND & AIMS: 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)-beta. 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-beta and the role of integrins with the alpha v subunit in this process. METHODS: Nave T cells were cultured with purified DCs from mesenteric lymph nodes (MLNs) or intestines of wild-type and alpha v 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 alpha v subunit was measured in purified subpopulations of DCs by quantitative polymerase chain reaction and immunoblot analyses. RESULTS: In vitro, CD103(+) DCs generated more Tregs in the presence of latent TGF-beta than other MLN DCs. Efficient generation of Tregs required expression of the integrin alpha v subunit by DCs; mice that lacked alpha v in immune cells did not convert nave T cells to intestinal Tregs in response to oral antigen. CD103(+) DCs derived from the MLNs selectively expressed high levels of integrin alpha v beta 8 compared with other populations of DCs. CONCLUSIONS: Expression of alpha v beta 8 is required for CD103(+) DCs to become specialized and activate latent TGF-beta and generate Tregs during the induction of tolerance to intestinal antigens in mice.