Osteopontin Promotes Protective Antigenic Tolerance against Experimental Allergic Airway Disease

Themis Alissafi, Evangelia Kourepini, Davina C. M. Simoes, Nikolaos Paschalidis, Maria Aggelakopoulou, Tim Sparwasser, Louis Boon, Hamida Hammad, Bart N. Lambrecht, Vily Panoutsakopoulou

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4 Citations (Scopus)
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Abstract

In the context of inflammation, osteopontin (Opn) is known to promote effector responses, facilitating a proinflammatory environment; however, its role during antigenic tolerance induction is unknown. Using a mouse model of asthma, we investigated the role of Opn during antigenic tolerance induction and its effects on associated regulatory cellular populations prior to disease initiation. Our experiments demonstrate that Opn drives protective antigenic tolerance by inducing accumulation of IFN-β–producing plasmacytoid dendritic cells, as well as regulatory T cells, in mediastinal lymph nodes. We also show that, in the absence of TLR triggers, recombinant Opn, and particularly its SLAYGLR motif, directly induces IFN-β expression in Ag-primed plasmacytoid dendritic cells, which renders them extra protective against induction of allergic airway disease upon transfer into recipient mice. Lastly, we show that blockade of type I IFNR prevents antigenic tolerance induction against experimental allergic asthma. Overall, we unveil a new role for Opn in setting up a tolerogenic milieu boosting antigenic tolerance induction, thus leading to prevention of allergic airway inflammation. Our results provide insight for the future design of immunotherapies against allergic asthma.
Original languageEnglish
Pages (from-to)1270-1282
JournalThe Journal of Immunology
Volume200
Issue number4
Early online date12 Jan 2018
DOIs
Publication statusPublished - 15 Feb 2018

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