10 The role of type I interferon in inflammatory rheumatic diseases: more questions than answers

Systemic lupus erythematosus (SLE) is a heterogeneous disease characterised by abnormalities in cellular and humoral immunity.The clinical complexity of SLE patients also comprise dysregulation of both the innate and adaptive immune responses, 1 leading to the breakdown of tolerance, production of autoantibodies, and deposition of immune complexes in tissues.This in turn leads to the activation of complement and the accumulation of neutrophils, monocytes and self-reactive T and Blymphocytes.Research into the pathogenesis of SLE offers a nexus of gene expression, cell signalling and cellular responses that can present with different degrees of dysregulation among patients with SLE.Key cytokines in SLE comprise, among others, Type I interferon (IFN), Type II IFN, interleukin (IL)-6, IL-12/23, IL-17 and B lymphocyte stimulator (BAFF/BlyS), which highlight the clinical and molecular heterogeneity of SLE. 2 Further abnormalities include alterations in the expression of IFN inducible chemokines, such as C-X-C motif chemokine ligand (CXCL) 10 and C-C motif chemokine ligand (CCL) 19 known to correlate with disease activity.Additionally, alterations are observed in the expression of cytokines related to leucocyte, neutrophil and macrophage trafficking, such as IL-6 and others.Two key advancements in SLE treatment target specific cytokine pathways: anifrolumab, 3 which inhibits Type I IFN receptor (IFNAR), and belimumab, 4 which targets BAFF/BlyS.The approvals of these medicines highlight the importance of these pathways in SLE pathogenesis.Based on this and recent insights in the cytokine network, including intracellular pathways targeting (i.e.janus kinase [JAK]-signal transducer and activator of transcription [STAT], and tyrosine kinase 2 [Tyk2]) as well as transcription factors (i.e.aiolos and ikaros), hold promise for potential future treatment options. 5This may serve to not only better control clinical lupus activity but also address the root causes of the disease, leading to potential for remission or cure.