| Title | Type I IFN drives unconventional IL-1β secretion in lupus monocytes. |
| Publication Type | Journal Article |
| Year of Publication | 2024 |
| Authors | Caielli S, Balasubramanian P, Rodriguez-Alcazar J, Balaji U, Robinson L, Wan Z, Baisch J, Smitherman C, Walters L, Sparagana P, Nehar-Belaid D, Marches R, Nassi L, Stewart K, Fuller J, Banchereau JF, Gu J, Wright T, Pascual V |
| Journal | Immunity |
| Date Published | 2024 Oct 03 |
| ISSN | 1097-4180 |
| 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 pyroptosis but relied on IFN-inducible myxovirus-resistant protein 1 (MxA), which facilitated the incorporation of mIL-1β into a trans-Golgi network (TGN)-mediated secretory pathway. RBC internalization identified a subset of blood Mo expressing IFN-stimulated genes (ISGs) that released mIL-1β and expanded in SLE patients with active disease. |
| DOI | 10.1016/j.immuni.2024.09.004 |
| Custom 1 | |
| Alternate Journal | Immunity |
| PubMed ID | 39378884 |