Type I IFN drives unconventional IL-1β secretion in lupus monocytes.

ABSTRACT: Opsonization of red blood cells that retain mitochondria (Mito⁺ RBCs), a feature of systemic lupus erythematosus (SLE), triggers type I interferon (IFN) production in macrophages. We report that monocytes (Mos) co-produce IFN and mature interleukin-1β (mIL-1β) upon Mito⁺ RBC opsonization. IFN expression depended on cyclic GMP-AMP synthase (cGAS) and RIG-I-like receptors' (RLRs) sensing of Mito⁺ RBC-derived mitochondrial DNA (mtDNA) and mtRNA, respectively. Interleukin-1β (IL-1β) production was initiated by the RLR antiviral signaling adaptor (MAVS) pathway recognition of Mito⁺ RBC-derived mtRNA. This led to the cytosolic release of Mo mtDNA, which activated the inflammasome. Importantly, mIL-1β secretion was independent of gasdermin D (GSDMD) and

SUBMITTER: Caielli S 

PROVIDER: S-EPMC11563874 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature