Ripoll Llagostera, ÈliaRamon, Laura deBordignon Draibe, JulianaMerino, AnaBolaños, NúriaGomà, MontseCruzado, Josep Ma.Grinyó Boira, Josep M.Torras Ambròs, Joan2018-02-202018-02-202016-06-081478-6362https://hdl.handle.net/2445/120023Es va publicar un erratum de l'article a: Arthritis Research & Therapy, 2016, vol. 18 , num. 1, p. 152Background: Lupus nephritis (LN) is a complex chronic autoimmune disease of unknown etiology characterized by loss of tolerance against several self-antigens. Cytokines are known to be central players in LN pathogenesis. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is one important pathway that mediates signal transduction of several cytokines. In this study, we examined the pathogenic role of this pathway and how CP-690,550 treatment influences LN outcome. Methods: Six-month-old NZB/NZWF1 mice were divided into two different treatment groups: (1) control animals given vehicle treatment, cyclophosphamide, and mycophenolate mofetil treatment as positive controls of the therapy and (2) mice treated with CP-690,550, a JAK3 inhibitor. Mice were treated for 12 weeks. We evaluated renal function, anti-double-stranded DNA (anti-dsDNA) antibody, renal histology changes, kidney complement and immunoglobulin G (IgG) deposits, T-cell and macrophage infiltration, kidney inflammatory gene expression, and circulating cytokine changes. Results: CP-690,550 treatment significantly reduced proteinuria and improved renal function and histological lesions of the kidney. Compared with vehicle-treated animals, those undergoing CP-690,550 treatment showed significantly diminished anti-dsDNA antibody and complement component C3 and IgG deposition in glomeruli. We also observed a significant reduction of T-cell and macrophage infiltration. Kidney gene expression revealed a reduction in inflammatory cytokines and complement and related macrophage-attracting genes. Circulating inflammatory cytokines were also reduced with treatment. Conclusions: On the basis of our results, we conclude that the JAK-STAT pathway is implicated in the progression of renal inflammation in NZB/WF1 mice and that targeting JAK3 with CP-690,550 is effective in slowing down the course of experimental LN. Thus, CP-690,550 could become a new therapeutic tool in LN and other autoimmune diseases.12 p.application/pdfengcc-by (c) Ripoll Llagostera, Èlia et al., 2016http://creativecommons.org/licenses/by/3.0/esLupusMalalties autoimmunitàriesCitoquinesRatolins (Animals de laboratori)LupusAutoimmune diseasesCytokinesMice (Laboratory animals)info:eu-repo/semantics/article6663802018-02-20info:eu-repo/semantics/openAccess27278657