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

Davina Camargo Madeira Simoes*, Nikolaos Paschalidis, Evangelia Kourepini*, Vily Panoutsakopoulou

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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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 melanoma tumor growth. In this process, pDCs are crucial. Finally, SLAYGLR enhances pDC development from bone marrow progenitors. These findings open new questions on the roles of sOpn and integrin α4 during homeostasis and inflammation. The newly identified integrin/IFN-β axis may be implicated in a wide array of immune responses.
Original languageEnglish
Article numbere202102055
Pages (from-to)1-19
Number of pages19
JournalJournal of Cell Biology
Volume221
Issue number9
Early online date25 Jul 2022
DOIs
Publication statusPublished - 25 Jul 2022

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