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TFEB and TFE3 regulate STING1-dependent immune responses by controlling type I interferon signaling [Q48645_RNAseq]

GSE281221 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2025/04/08 Platform GPL19057
Summary
STING1 is an essential component of the innate immune defense against a wide variety of pathogens. Whereas induction of Type I interferon (IFN) responses is one of the best-defined functions of STING1, our transcriptomic analysis revealed IFN-independent activities of STING1 in macrophages, including transcriptional upregulation of numerous lysosomal and autophagic genes. This upregulation was mediated by the STING1-induced activation of the transcription factors TFEB and TFE3, and led to increased autophagy, lysosomal biogenesis, and lysosomal acidification. TFEB and TFE3 also modulated IFN-dependent STING1 signaling by controlling IRF3 activation. IFN production and cell death were increased in TFEB and TFE3 depleted iBMDMs. Conversely, TFEB over-expression led to reduced IRF3 activation and an almost complete inhibition of interferon synthesis and secretion, resulting in decrease caspase-3 activation and increased cell survival. Our study reveals a key role of TFEB and TFE3 as regulators of STING1-mediated innate antiviral immunity.
Published in
TFEB and TFE3 regulate STING1-dependent immune responses by controlling type I interferon signaling
Tapia PJ, Martina JA, Contreras PS et al. · Autophagy 2025 · PMID 40195022 · doi:10.1080/15548627.2025.2487036
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Also filed as BioProject PRJNA1182755 and SRA study SRP543607. Searching any of these in the dataset finder brings you back here.

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