Imaging · study · 2026
Synovial Th17 transdifferentiation into exTh17 sustains chronic IL-17-independent inflammatory arthritis [Visium]
Listed in NCBI GEO
Rheumatoid arthritis (RA) is the most common systemic autoimmune disease.
Description
T helper 17 (Th17) cells are found in the inflamed synovium in RA and believed to play a pathogenic role. However, IL-17 targeted interventions have shown limited efficacy in established RA.
Inflammation can induce Th17 transdifferentiation into IL-17 negative Th1 or Tr1 like exTh17. To assess the potential phenotype and role of exTh17 in inflammatory arthritis, we performed Th17 fate mapping studies in the SKG mouse model of RA. We generated triTh17-SKG (IL-17Cre.IfngYFP.Il10eGFP.R26tdTomfl.Zap70SKG) mice and leveraged them to show that in arthritic mice synovial Th17 transdifferentiate into IFNγ- and IL-10- exTh17 which become the most prominent CD4 population in chronic arthritis.
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These exTh17 cells are more arthritogenic than Th17, and able to sustain arthritis that is IL-17 independent but enriched with IL-6 and TNF, two known RA-promoting cytokines. Synovial exTh17 present a unique gene signature including upregulation of CD44 and S1PR4 that has correlates in the profile of CD4 T cells found in human RA synovium. We further demonstrate that a crosstalk with synoviocytes and S1P signaling promote Th17-exTh17 conversion and that CD44 – another known target for RA- is necessary for the arthritogenic effect of exTh17.
Our study suggests that the synoviocyte expansion which occurs during RA progression can drive progressive conversion of Th17 into exTh17, which in turn sustain inflammation that has hallmarks of human established RA.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE232nnn/GSE232734 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE232734 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA973666 ncbi.nlm.nih.gov/bioproject/PRJNA973666 ↗
project · from NCBI GEO
- PubMed 41202149 pubmed.ncbi.nlm.nih.gov/41202149 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Homo sapiens · Other
- From keywords
- Life Sciences
- Inferred from text
- Disease 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE232734 | 11 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:other | 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 |