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

Camargo Madeira Simoes, Davina, Paschalidis, Nikolaos, Kourepini, Evangelia and Panoutsakopoulou, Vily (2022) An integrin axis induces IFN-β production in plasmacytoid dendritic cells. Journal of Cell Biology, 221 (9). e202102055. ISSN 0021-9525

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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.

Item Type: Article
Additional Information: Funding information: This paper is dedicated to the memory of our beloved professor V. Panoutsakopoulou (1967–2018). The authors thank M. Bessa for assisting with manuscript editing, A. Apostolidou for flow-cytometric sorting of cellular populations, E. Rigana for imaging acquisition and processing, and A. Koniaris for assistance with software handling. The authors also thank Amgen and Celldex Therapeutics for kindly providing hFlt3L. The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Program (FP7/2007-2013)/European Research Council Grant Agreement no. (243322; V. Panoutsakopoulou). E. Kourepini and N. Paschalidis are the recipients of State Scholarship Foundation postdoctoral scholarships (2017–2019).
Subjects: C500 Microbiology
C700 Molecular Biology, Biophysics and Biochemistry
Department: Faculties > Health and Life Sciences > Applied Sciences
Depositing User: Elena Carlaw
Date Deposited: 19 Oct 2021 11:21
Last Modified: 05 Aug 2022 09:08

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