Erythroid mitochondrial retention triggers myeloid-dependent type I interferon in human SLE.

ABSTRACT: Emerging evidence supports that mitochondrial dysfunction contributes to systemic lupus erythematosus (SLE) pathogenesis. Here we show that programmed mitochondrial removal, a hallmark of mammalian erythropoiesis, is defective in SLE. Specifically, we demonstrate that during human erythroid cell maturation, a hypoxia-inducible factor (HIF)-mediated metabolic switch is responsible for the activation of the ubiquitin-proteasome system (UPS), which precedes and is necessary for the autophagic removal of mitochondria. A defect in this pathway leads to accumulation of red blood cells (RBCs) carrying mitochondria (Mito⁺ RBCs) in SLE patients and in correlation with disease activity. Antibody-mediated internalization of Mito⁺ RBCs induces type I interferon (IFN) production t

SUBMITTER: Caielli S 

PROVIDER: S-EPMC8380737 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature