title: A new role for myeloid HO-1 in the innate to adaptive crosstalk and immune homeostasis.
abstract: Increasing evidence supports the presence of a dynamic crosstalk between innate and adaptive immunity with a pivotal role played by pathways governing innate immune responses. TLRs (Toll-like receptors) and RLHs (retinoic acid-inducible gene I [RIG-I]-like helicases) are known to play a key role in these processes. A molecule of high significance in the protection against innate and adaptive immune aberrations is heme oxygenase 1 (HO-1). HO-1 is a microsomal enzyme that catalyses the degradation of heme to iron, carbon monoxide and bilirubin. These by-products appear to be the key mediators of its anti--inflammatory and cytoprotective action, mainly through the downregulation of pro-inflammatory and upregulation of anti-inflammatory molecules. Recent data from our lab support the presence of an additional direct effect of myeloid HO-1 on innate immune conditioning, and more specifically on the TLR3/TLR4/RIG-I pathway. In myeloid cells, HO-1 forms a complex with the transcription factor IRF3 (Interferon regulating factor 3) and is required for IRF3 phosphorylation and consequent type-I interferon and chemokine gene induction. Myeloid HO-1-deficient mice show reduced expression of IRF3 target genes and altered responses to infectious and organ-specific auto-immune diseases. This new frame of understanding HO-1 function should also be important for the future design of novel interventions differentially targeting the enzymatic versus the IRF3 modulating properties of HO-1.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Koliaraki
authors.forename: George
authors.initials: G
authors.lastname: Kollias
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000276:immunology; D006418:Heme / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000201:enzymology / Q000276:immunology*; D010766:Phosphorylation / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015533:Transcriptional Activation / Q000276:immunology
chemical_list: D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I; C494233:Irf3 protein, mouse; C519703:TLR3 protein, mouse; C493487:Tlr4 protein, mouse; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D006418:Heme; D051547:Heme Oxygenase-1; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases