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.
Ivashkiv
Lionel B
LB
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
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