Omics · study · 2026
Reduced Accumulation of Chemokine-Specific CD4 + T Cells in the Lungs of BeO- Exposed HLA-DP2 Transgenic Mice Deficient in CCL3/4 or Treated with Novel HLA- DP2/CCL-CAR-T Cells
Listed in NCBI GEO
Chemokines play an important role in the recruitment and activation of immune cells and in forming inflammatory cellular aggregates.
Description
However, how these chemokines and chemokines- specific CD4 + T cells contribute to the pathogenesis of CBD is not well defined. RNA sequencing of CD4 + T cells showed functional heterogeneity among chemokine specific- tissue-resident CCL4 tetramer-positive CD4 + T cells (CD44 + Tet + ).
CD44 + Tet + cells display increased IFNγ and IL17 gene expression compared to the CD44 - Tet - (naïve) CD4 + T cells. Over-representation analysis of genes showed pathways involved in inflammation and cholesterol metabolism are significantly increased in CD44 + Tet + cells. Next, we showed that innate immune response in Be 2+ exposed HLA-DP2 Tg WT and CCL3-deficient mice (CCL3 - /- ) was not different, while a significant decrease in total, antigen-specific CD4 + T cells and IFNγ-producing CD4 + T cells was observed in CCL3 -/- mice.
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We also noticed fewer peribronchovascular aggregates in the lungs of Be 2+ exposed CCL3 -/- mice, suggesting reduced inflammation. In BeO-exposed lungs, enhanced CCL3 expression was observed in macrophages and dendritic cells (DCs). Further, using bone marrow chimeric mice, we established the role of hematopoietic and DCs in controlling Be-induced CCL3 and CCL4 responses in the lungs.
Besides the chemokines, we also found that HLA-DP2 Tg mice deficient in TNF-α or treated with HLA-DP-CCL4-CAR-T cells show reduced presence of chemokine-specific CD4 + T cells in the lungs. In conclusion, our findings reveal an important role of DCs and TNF-α in maintaining CCL3/4-specific CD4 + T cell responses in CBD and also provide CAR-T cells as an alternative therapy for regulating CCL3/4-specific CD4 + T cell responses in CBD.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE325nnn/GSE325899 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE325899 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1442181 ncbi.nlm.nih.gov/bioproject/PRJNA1442181 ↗
project · from NCBI GEO
- PubMed 42262522 pubmed.ncbi.nlm.nih.gov/42262522 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- RNA sequencing 75% · Sequencing 75%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE325899 | 11 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| 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[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| 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 |