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SPARC regulation of PMN clearance protects from pristane-induced lupus and rheumatoid arthritis.
Sangaletti, Sabina; Botti, Laura; Gulino, Alessandro; Lecis, Daniele; Bassani, Barbara; Portararo, Paola; Milani, Matteo; Cancila, Valeria; De Cecco, Loris; Dugo, Matteo; Tripodo, Claudio; Colombo, Mario P.
Afiliação
  • Sangaletti S; Molecular Immunology Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
  • Botti L; Molecular Immunology Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
  • Gulino A; Tumor Immunology Unit, University of Palermo, Palermo, Italy.
  • Lecis D; Molecular Immunology Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
  • Bassani B; Molecular Immunology Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
  • Portararo P; Molecular Immunology Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
  • Milani M; Molecular Immunology Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
  • Cancila V; Tumor Immunology Unit, University of Palermo, Palermo, Italy.
  • De Cecco L; Platform of Integrated Biology, Department of Applied Research and Technology Development, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
  • Dugo M; Platform of Integrated Biology, Department of Applied Research and Technology Development, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
  • Tripodo C; Tumor Immunology Unit, University of Palermo, Palermo, Italy.
  • Colombo MP; Molecular Immunology Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
iScience ; 24(6): 102510, 2021 Jun 25.
Article em En | MEDLINE | ID: mdl-34142027
The secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein with unexpected immunosuppressive function in myeloid cells. We investigated the role of SPARC in autoimmunity using the pristane-induced model of lupus that, in mice, mimics human systemic lupus erythematosus (SLE). Sparc -/- mice developed earlier and more severe renal disease, multi-organ parenchymal damage, and arthritis than the wild-type counterpart. Sparc +/- heterozygous mice showed an intermediate phenotype suggesting Sparc gene dosage in autoimmune-related events. Mechanistically, reduced Sparc expression in neutrophils blocks their clearance by macrophages, through defective delivery of don't-eat-me signals. Dying Sparc -/- neutrophils that escape macrophage scavenging become source of autoantigens for dendritic cell presentation and are a direct stimulation for γδT cells. Gene profile analysis of knee synovial biopsies from SLE-associated arthritis showed an inverse correlation between SPARC and key autoimmune genes. These results point to SPARC down-regulation as a leading event characterizing SLE and rheumatoid arthritis pathogenesis.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2021 Tipo de documento: Article