Modulation of murine lupus by Aconitate Decarboxylase 1
نویسندگان
چکیده
Abstract Mitochondrial synthesis of itaconate by myeloid cells (monocytes and macrophages) is mediated the TCA cycle enzyme Aconitate Decarboxylase 1 (Acod1). Upregulation Acod1–itaconate pathway, occurs after activation various Toll-like receptors (TLRs) or cytokine stimulation (TNF type I Interferons). While anti-inflammatory effects Acod1 – Itaconate pathway have been previously reported (e.g. decreases in IL-6 IL-1β synthesis) contribution impairments endogenous systemic lupus erythematosus (SLE) remain poorly characterized. First, we explored characterized expression bone marrow monocyte-derived macrophages (BMDM MDM, respectively) following vitro imiquimod (IMQ) treatment. Then, investigated role modulation development severity TLR-7 induced using IMQ model. 10-week-old wild −/−mice were treated with topical cream for 5 weeks to induce an SLE phenotype. We found that protein BMDM MDM 12 hours stimulation, this induction partially dependent on IFNRa1 signaling. Moreover, −/−BMDM h displayed higher mRNA il6, il1b, il18, ccl2, cxcl2, cxcl9, together increase pro-IL-1β levels. production also increased. After vivo treatment, a concentration circulating anti-dsDNA autoantibodies but decrease splenomegaly compared WT mice. These results, demonstrate putative Acod1-itaconate regulation autoimmunity. This work support NIH/NIAMS Intramural Research Program
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ژورنال
عنوان ژورنال: Journal of Immunology
سال: 2023
ISSN: ['1550-6606', '0022-1767']
DOI: https://doi.org/10.4049/jimmunol.210.supp.78.01