{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE325nnn/GSE325899/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE325899"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"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","description":"Chemokines play an important role in the recruitment and activation of immune cells and in forming inflammatory cellular aggregates. 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. 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.","dates":{"publication":"2026/05/18"},"accession":"GSE325899","cross_references":{"GSM":["GSM9616320","GSM9616319","GSM9616316","GSM9616315","GSM9616318","GSM9616317","GSM9616312","GSM9616314","GSM9616313"],"GPL":["21103"],"GSE":["325899"],"taxon":["Mus musculus"]}}