Omics · study · 2026
The autoantigen TRIM21 assembles proinflammatory immune complexes following lytic cell death
Listed in NCBI GEO
Sjögren’s disease (SjD) causes localized and systemic inflammation and autoantibody production against intracellular proteins such as TRIM21/Ro52 (tripartite motif-containing protein 21).
Description
TRIM21, an E3 ubiquitin ligase, binds antibody Fc domains on opsonized pathogens that have escaped extracellular immunity and entered the cytosol. TRIM21 then ubiquitinates these pathogens, driving their proteasomal degradation.
How TRIM21 becomes an autoantigen remains unclear. We show that TRIM21 is released upon lytic cell death (pyroptosis/necroptosis) but not apoptosis. Although many cytosolic proteins are released by dead cells, liberated TRIM21 is distinct: its high antibody affinity enables binding to Fc domains of circulating immunoglobulins, forming large immune complexes (ICs).
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These ICs increase in SjD, where anti-TRIM21 autoantibodies interact with released TRIM21 via Fc and F(ab′)2. TRIM21-ICs are taken up by macrophages, which, in high interferon environments, drive proinflammatory responses, antigen presentation, and metabolic changes. Thus, TRIM21 may perpetuate inflammation and autoantigen presentation, resulting in high immunogenicity.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE318nnn/GSE318852 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE318852 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1420722 ncbi.nlm.nih.gov/bioproject/PRJNA1420722 ↗
project · from NCBI GEO
- PubMed 41996473 pubmed.ncbi.nlm.nih.gov/41996473 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Disease 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE318852 | 14 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:9606 | 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 |