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Single-cell RNA sequencing analysis of the effect of 4-octyl itaconate administration on gene expression in immune cells isolated from traumatic brain injury mice brain

ABSTRACT: 4-octyl itaconate regulates immune response of brain immune cells following traumatic brain injury.

ORGANISM(S): Mus musculus

PROVIDER: GSE272808 | GEO | 2024/07/27

REPOSITORIES: GEO

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RNA-seq Transcriptomic Analysis of 4-octyl itaconate Repressing Myogenic Differentiation

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Single-cell RNA sequencing analysis of the effect of 4-octyl itaconate administration on gene expression in immune cells isolated from traumatic brain injury mice brain

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Expression data from hiPSC derived WT and ISG15 KO endothelial cells stimulated with interferon-a and treated with itaconic acid, dimethyl itaconate, 4-octyl itaconate and ruxolitinib

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Project description:<p>The Krebs cycle-derived metabolite itaconate, whose production is catalyzed by immune response gene 1 (IRG1), has excellent potential to link immunity and metabolism in activated macrophages through alkylation or competitive inhibition of target proteins. In support of this, our previous study demonstrated that the stimulator of interferon genes (STING) signaling platform functions as a hub in macrophage immunity and has a profound impact on the prognosis of sepsis. Interestingly, we found that itaconate, an endogenous immunomodulator, can significantly inhibit the activation of STING signaling. Moreover, 4-octyl itaconate (4-OI), which is a permeable itaconate derivative, could alkylate cysteine sites 65, 71, 88, and 147 of STING, thereby inhibiting its phosphorylation and downregulating the production of related inflammatory factors. Furthermore, itaconate and 4-OI inhibited the production of inflammatory factors in sepsis models. Our results have broadened the role of the IRG1-Itaconate axis in immunomodulation and highlighted itaconate and its derivatives as potential therapeutic agents in sepsis.</p>

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Effect of 4-octyl itaconate on gene expression of dendritic cells

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