An integrin axis induces IFN-β production in plasmacytoid dendritic cells.

ABSTRACT: Type I interferon (IFN) production by plasmacytoid dendritic cells (pDCs) has been mainly studied in the context of Toll-like receptor (TLR) activation. In the current report, we reveal that, in the absence of TLR activation, the integrin-binding SLAYGLR motif of secreted osteopontin (sOpn) induces IFN-β production in murine pDCs. This process is mediated by α4β1 integrin, indicating that integrin triggering may act as a subtle danger signal leading to IFN-β induction. The SLAYGLR-mediated α4 integrin/IFN-β axis is MyD88 independent and operates via a PI3K/mTOR/IRF3 pathway. Consequently, SLAYGLR-treated pDCs produce increased levels of type I IFNs following TLR stimulation. Intratumoral administration of SLAYGLR induces accumulation of IFN-β-expressing pDCs and efficiently suppresses mela

SUBMITTER: Simoes DCM 

PROVIDER: S-EPMC9354318 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature