@ARTICLE{10.3389/fimmu.2018.02081, AUTHOR={Gatto, Mariele and Luisetto, Roberto and Ghirardello, Anna and Cavicchioli, Laura and Codolo, Gaia and Biasiolo, Alessandra and Maggioni, Giuseppe and Saccon, Francesca and Beggio, Marianna and Cappon, Andrea and Venturini, Roberta and Pontisso, Patrizia and Doria, Andrea}, TITLE={SERPINB3 Delays Glomerulonephritis and Attenuates the Lupus-Like Disease in Lupus Murine Models by Inducing a More Tolerogenic Immune Phenotype}, JOURNAL={Frontiers in Immunology}, VOLUME={9}, YEAR={2018}, URL={https://www.frontiersin.org/articles/10.3389/fimmu.2018.02081}, DOI={10.3389/fimmu.2018.02081}, ISSN={1664-3224}, ABSTRACT={Objective: To explore the effects of SERPINB3 administration in murine lupus models with a focus on lupus-like nephritis.Methods: 40 NZB/W F1 mice were subdivided into 4 groups and intraperitoneally injected with recombinant SERPINB3 (7.5 μg/0.1 mL or 15 μg/0.1 mL) or PBS (0.1 mL) before (group 1 and 2) or after (group 3 and 4) the development of proteinuria (≥100 mg/dl). Two additional mice groups were provided by including 20 MRL/lpr mice which were prophylactically injected with SERPINB3 (10 mice, group 5) or PBS (10 mice, group 6). Time of occurrence and levels of anti-dsDNA and anti-C1q antibodies, proteinuria and serum creatinine, overall- and proteinuria-free survival were assessed in mice followed up to natural death. Histological analysis was performed in kidneys of both lupus models. The Th17:Treg cell ratio was assessed by flow-cytometry in splenocytes of treated and untreated MRL/lpr mice. Statistical analysis was performed using non parametric tests and Kaplan-Meier curves, when indicated.Results: Autoantibody levels and proteinuria were significantly decreased and time of occurrence significantly delayed in SERPINB3-treated mice vs. controls. In agreement with these findings, proteinuria-free and overall survival were significantly improved in SERPINB3-treated groups vs. controls. Histological analysis demonstrated a lower prevalence of severe tubular lesions in kidneys of group 5 vs. group 6. SERPINB3-treated mice showed an overall trend toward a reduced prevalence of severe lesions in both strains. Th17:Treg ratio was significantly decreased in splenocytes of MRL/lpr mice treated with SERPINB3, compared to untreated control mice.Conclusions: SERPINB3 significantly improves disease course and delays the onset of severe glomerulonephritis in lupus-prone mice, possibly inducing a more tolerogenic immune phenotype.} }