Systemic lupus erythematosus and the type I interferon system.
Patients with systemic lupus erythematosus (SLE) have ongoing interferon-alpha (IFN-alpha) production and serum IFN-alpha levels are correlated with both disease activity and severity. Recent studies of patients with SLE have demonstrated the presence of endogenous IFN-alpha inducers in such individuals, consisting of small immune complexes (ICs) containing IgG and DNA. These ICs act specifically on natural IFN-alpha-producing cells (NIPCs), often termed plasmacytoid dendritic cells (PDCs). Given the fact that the NIPC/PDC has a key role in both the innate and adaptive immune response, as well as the many immunoregulatory effects of IFN-alpha, these observations might be important for the understanding of the etiopathogenesis of SLE. In this review we briefly describe the biology of the type I IFN system, with emphasis on inducers, producing cells (especially NIPCs/PDCs), IFN-alpha actions and target immune cells that might be relevant in SLE. On the basis of this information and results from studies in SLE patients, we propose a hypothesis that explains how NIPCs/PDCs become activated and have a pivotal etiopathogenic role in SLE. This hypothesis also indicates new therapeutic targets in this autoimmune disease.
Rönnblom
Lars
L
Department of Medical Sciences, Section of Rheumatology, University Hospital, Uppsala, Sweden. Lars.Ronnblom@medsci.uu.se
Alm
Gunnar V
GV
D017951:Antigen Presentation; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007370:Interferon Type I / Q000037:antagonists & inhibitors / Q000502:physiology*; D016898:Interferon-alpha / Q000502:physiology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000276:immunology*
D007370:Interferon Type I; D016898:Interferon-alpha