title: Mislocalization of the interferon inducible protein IFI16 by environmental insults: implications in autoimmunity.
abstract: The nuclear DNA sensor IFI16, a member of PYHIN family of proteins, was previously studied for its role in cell cycle regulation, tumor suppression, apoptosis and DNA damage signaling. Autoantibodies against IFI16 are prevalent in the sera of patients with systemic autoimmunity, thus depicting physiological significance as an autoantigen. At present, the nuclear IFI16 protein has been thoroughly investigated for its role as an innate immune sensor involved in inflammasome signaling and viral restriction. While the sub-cellular localization of IFI16 during such events has been known, very little knowledge about its presence and significance in the extracellular space is available. Recently our group has discovered the presence of circulating IFI16 in the sera from systemic autoimmune patients indicating that in this setting it may be mislocalized form its nuclear site and secreted in the extracellular milieu. In this review, we will discuss the leakage of endogenous IFI16 that has been experimentally proved using in vivo and in vitro models. Also we will comment on the significance of mislocalized inflammasome components in the extracellular space and how it can be responsible for chronic inflammation.
authors.affiliation: Department of Translational Medicine, University of Eastern Piedmont, Via Solaroli 17, Novara 28100, Italy; Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Via Solaroli 17, Novara 28100, Italy.
authors.forename: Mandar
authors.initials: M
authors.lastname: Bawadekar
authors.affiliation: Department of Translational Medicine, University of Eastern Piedmont, Via Solaroli 17, Novara 28100, Italy; Department of Public Health and Pediatric Sciences, University of Turin, Via Santena 9, Turin 10126, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: De Andrea
authors.affiliation: Department of Translational Medicine, University of Eastern Piedmont, Via Solaroli 17, Novara 28100, Italy; Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Via Solaroli 17, Novara 28100, Italy.
authors.forename: Marisa
authors.initials: M
authors.lastname: Gariglio
authors.affiliation: Department of Public Health and Pediatric Sciences, University of Turin, Via Santena 9, Turin 10126, Italy. Electronic address: santo.landolfo@unito.it.
authors.forename: Santo
authors.initials: S
authors.lastname: Landolfo
mesh_terms: D000067531:Alarmins / Q000276:immunology / Q000378:metabolism; D017209:Apoptosis; D001323:Autoantibodies / Q000097:blood; D015551:Autoimmunity; D003587:Cytomegalovirus / Q000472:pathogenicity; D005110:Extracellular Space / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D058847:Inflammasomes / Q000276:immunology / Q000378:metabolism; D007369:Interferon Inducers / Q000276:immunology; D009687:Nuclear Proteins / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D010750:Phosphoproteins / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D014466:Ultraviolet Rays
chemical_list: D000067531:Alarmins; D001323:Autoantibodies; D058847:Inflammasomes; D007369:Interferon Inducers; D009687:Nuclear Proteins; D010750:Phosphoproteins; C076700:IFI16 protein, human
keywords: DAMPs; DNA sensor; Danger signal; IFI16; Mislocalization