Omics · study · 2026
SESN1 attenuates innate immune response by promoting MAVS autophagic degradation
Listed in NCBI GEO
Mitochondrial antiviral signaling protein (MAVS), as a central hub protein in RNA-triggered innate immune response, plays a crucial role in antiviral immunity.
Description
The protein stability of MAVS must be strictly regulated to maintain immune homeostasis. However, the exact molecular mechanisms regulating the stability of MAVS remains poorly understood.
Here, we reported that SESN1 acts as a critical negative regulator of MAVS by promoting MAVS autophagic degradation to regulate innate immune response. Intriguingly, the expression of SESN1 was dynamic to maintain innate immune homeostasis after RNA virus VSV or IAV PR8 infection. SESN1 mRNA level was decreased at early stage and was rebounded at late stage, which released SESN1-mediated MAVS inhibition to clear virus at early stage and prevent hyper-inflammation at late stage.
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Moreover, SESN1-deficient mice showed stronger ability against virus infection compared to control mice when challenged with VSV or IAV PR8. Notably, we observed that the expression of SESN1 was markedly downregulated and negatively correlated with cytokines level in patients with influenza. Importantly, the replenishment of SESN1 effectively inhibited cytokine production in the PBMCs of patients with influenza.
Mechanistically, SESN1 interacted with MAVS and potentiated MAVS autophagic degradation via SQSTM1. Taken together, these findings revealed a novel regulatory role of SESN1 in innate antiviral immune response by regulating MAVS. Targeting SESN1 might be a potential therapeutic strategy for treating RNA virus infectious disease.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE299nnn/GSE299504 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE299504 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1274877 ncbi.nlm.nih.gov/bioproject/PRJNA1274877 ↗
project · from NCBI GEO
- PubMed 42647126 pubmed.ncbi.nlm.nih.gov/42647126 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Disease 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE299504 | 15 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |