Potential role of IFNα in adult lupus.
Patients with lupus have a continuous production of IFNα and display an increased expression of IFNα-regulated genes. The reason for the ongoing IFNα synthesis in these patients seems to be an activation of plasmacytoid dendritic cells (pDCs) by immune complexes (ICs), consisting of autoantibodies in combination with DNA-containing or RNA-containing autoantigens. The mechanisms behind the activation of pDCs by such ICs have to some extent been elucidated during the last years. Thus, interferogenic ICs are internalized via the FcγRIIa expressed on pDCs, reach the endosomes and stimulate Toll-like receptor (TLR) 7 or 9, which subsequently leads to IFNα gene transcription. Variants of genes involved in both the IFNα synthesis and response have been linked to an increased risk to develop lupus. Among these genes are interferon regulatory factor 5 (IRF5), which is involved in TLR signaling, and the signal transducer and activator of transcription 4 (STAT4) that interacts with the type I interferon receptor. Produced IFNα may at least partially be responsible for several of the observed alterations in the immune system of lupus patients and contribute to the autoimmune disease process, which will be discussed in the present review. How produced IFNα can contribute to some clinical manifestations will briefly be described, as well as the possible consequences of this knowledge in clinical practice for disease monitoring and therapy.
Rönnblom
Lars
L
Department of Medical Sciences, Section of Rheumatology, Uppsala University, Uppsala University Hospital, Entrance 40, Uppsala, Sweden. Lars.Ronnblom@medsci.uu.se
D000328:Adult; D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics; D015415:Biomarkers; D003713:Dendritic Cells / Q000378:metabolism; D004195:Disease Models, Animal; D011992:Endosomes / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology; D016898:Interferon-alpha / Q000096:biosynthesis / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D008181:Lupus Nephritis / Q000209:etiology / Q000276:immunology; D051379:Mice; D018448:Models, Immunological; D058990:Molecular Targeted Therapy; D017452:Receptors, IgG / Q000378:metabolism; D012306:Risk; D050797:STAT4 Transcription Factor / Q000235:genetics / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000276:immunology
D000974:Antibodies, Antinuclear; D001324:Autoantigens; D015415:Biomarkers; C080568:Fc gamma receptor IIA; C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors; D016898:Interferon-alpha; D017452:Receptors, IgG; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; C495348:TLR7 protein, human; C495371:TLR9 protein, human; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9
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