Type I interferon modulation of cellular responses to cytokines and infectious pathogens: potential role in SLE pathogenesis.
Type I interferons (IFNs) are pleiotropic cytokines that have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). A key aspect of type I IFN biology is that previous exposure to type I IFNs alters subsequent cellular responses to extracellular stimuli. Type I IFNs may either prime cells for stronger responses to viruses, bacterial pathogens and cytokines such as IL-6 and IFN-gamma, or may suppress cellular responses to LPS and TNFalpha. Herein, we review type I IFN signal transduction via the Jak-STAT pathway, and mechanisms by which type I IFNs prime or suppress responses to environmental factors. We develop a hypothesis that type I IFN-dependent priming/enhancement of cellular responses to pro-inflammatory cytokines such as IFNgamma and IL-6 contributes to pathogenesis of SLE. In addition, cross-regulation between type I IFNs and TNFalpha and its potential role in SLE pathogenesis is discussed.
Department of Medicine, Hospital for Special Surgery, Weill Medical College of Cornell University, 535 East 70th Street, New York, NY 10021, USA. ivashkivl@hss.edu
Lionel B
LB
Ivashkiv
D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000096:biosynthesis / Q000276:immunology*; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D004268:DNA-Binding Proteins; D007370:Interferon Type I; D011518:Proto-Oncogene Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2