SPARC regulation of PMN clearance protects from pristane-induced lupus and rheumatoid arthritis.

ABSTRACT: 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 ^<

SUBMITTER: Sangaletti S 

PROVIDER: S-EPMC8188360 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature