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| Status |
Public on Oct 07, 2024 |
| Title |
Type I Interferon promotes MxA-dependent IL-1b release in SLE monocytes |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Systemic lupus erythematosus (SLE) is characterized by upregulation of Type Ι Interferon (IFN) and widespread inflammation. However, blocking the IFN pathway benefits a fraction of patients, pointing to additional pathogenic players. Here we describe monocytes (Mo) undergoing erythrophagocytosis and co-expressing IFN-inducible genes (ISGs) and interleukin-1b (IL-1b) in patients with active disease. This phenotype is recapitulated in vitro upon internalization of red blood cells carrying mitochondria (Mito+ RBCs), a feature of SLE. While ISG expression requires the interaction between Mito+ RBC-derived mitochondrial DNA (mtDNA) and cGAS, the production of IL-1b entails Mito+ RBC-derived mitochondrial RNA (mtRNA) triggering RIG-I-like receptor (RLR) activation. This leads to the cytosolic release of Mo-derived mtDNA and activation of the NLRP3 inflammasome. Importantly, the Type I IFN-inducible protein myxovirus resistant protein 1 (MxA) enables IL-1b release by routing this cytokine into a trans-Golgi network (TGN)-mediated unconventional secretory pathway. As Type I IFN and IL-1b are thought to counter-regulate each other, our study highlights an unprecedented synergy between these two cytokine pathways in SLE.
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| Overall design |
Human Monocytes (Mo) or BLaER1 Mo were cocultured with CFSE labeled red blood cells carrying (Mito+) or not carrying (Mito-) RBCs in complete RPMI medium. 18 hr later Mo or BLaER1 Mo internalizing RBCs were FACS sorted and processesed for RNAseq analysis
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| Contributor(s) |
Caielli S, Balasubramanian P, Balaji U, Wan Z, Baisch J, Walters L, Smitherman C, Nehar-Belaid D, Marches R, Nassi L, Stewart K, Fuller J, Banchereau JF, Gu J, Wright T, Pascual V |
| Citation(s) |
39378884 |
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| Submission date |
Aug 16, 2022 |
| Last update date |
Jan 06, 2025 |
| Contact name |
Simone Caielli |
| E-mail(s) |
sic2011@med.cornell.edu
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| Organization name |
Weill Cornell Medicine
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| Department |
Department of Pediatrics
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| Street address |
413 E 69th Street
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA869965 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE211361_RAW.tar |
1.1 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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