IFP35 Is a Relevant Factor in Innate Immunity, Multiple Sclerosis, and Other Chronic Inflammatory Diseases: A Review

Abstract

Discovered in 1993 by Bange et al., the 35-kDa interferon-induced protein (IFP35) is a highly conserved cytosolic interferon-induced leucine zipper protein with a 17q12-21 coding gene and unknown function. Belonging to interferon stimulated genes (ISG), the IFP35 reflects the type I interferon (IFN) activity induced through the JAK-STAT phosphorylation, and it can homodimerize with N-myc-interactor (NMI) and basic leucine zipper transcription factor (BATF), resulting in nuclear translocation and a functional expression. Casein kinase 2-interacting protein-1 (CKIP-1), retinoic acid-inducible gene I (RIG-I), and laboratory of genetics and physiology 2 Epinephelus coioides (EcLGP2) are thought to regulate IFP35, via the innate immunity pathway. Several in vitro and in vivo studies on fish and mammals have confirmed the IFP35 as an ISG factor with antiviral and antiproliferative functions. However, in a mice model of sepsis, IFP35 was found working as a damage associated molecular pattern (DAMP) molecule, which enhances inflammation by acting in the innate immune-mediated way. In human pathology, the IFP35 expression level predicts disease outcome and response to therapy in Multiple Sclerosis (MS), reflecting IFN activity. Specifically, IFP35 was upregulated in Lupus Nephritis (LN), Rheumatoid Arthritis (RA), and untreated MS. However, it normalized in the MS patients undergoing therapy. The considered data indicate IFP35 as a pleiotropic factor, suggesting it as biologically relevant in the innate immunity, general pathology, and human demyelinating diseases of the central nervous system.