{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE309nnn/GSE309229/"]},"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=GSE309229"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"CXCR3 ameliorates neutrophils-dependent disease severity in SARS-CoV-2 infection by regulating CD4+ T cell recruitment","description":"Understanding the host immune response to SARS-CoV-2 infection is critical for developing effective immunotherapeutic interventions. Using bulk RNA sequencing of lung tissue from mock-infected and mouse-adapted SARS-CoV-2 strain MA-10-infected mice, we identified CXCL9, CXCL10, and CXCL11 as among the most upregulated transcripts. Notably, their shared receptor, CXCR3, was also upregulated, suggesting activation of the CXCL9/10/11–CXCR3 axis in the lungs. Using spectral flow cytometry, we observed that the increased recruitment of CXCR3⁺ immune cells, particularly T cells, innate lymphoid cells (ILCs), and macrophages, correlated with milder disease outcome. Blocking CXCR3 signaling using monoclonal antibodies resulted in worsened disease, which was accompanied by reduced recruitment of T cells, ILCs, and macrophages, and a marked increase in neutrophil infiltration. Depletion of neutrophils using αLy6G antibodies in CXCR3-blocked mice alleviated disease severity, indicating that CXCR3 signaling mitigated neutrophil-driven pathology. CXCR3 blockade failed to exacerbate disease in RAG2⁻/⁻ mice, suggesting that CXCR3-mediated protection requires adaptive immune cells. Adoptive transfer of CD4⁺ T cells from wild type (WT), but not CXCR3⁻/⁻, mice conferred protection in RAG2⁻/⁻ mice. Together, our findings establish a protective role for CXCR3-recruited T cells blocking neutrophil infiltration in the lung, highlighting the mechanistic importance of the CXCL9/10/11–CXCR3 axis in protecting the lung from SARS-CoV-2 infection.","dates":{"publication":"2026/06/08"},"accession":"GSE309229","cross_references":{"GSM":["GSM9263435","GSM9263434","GSM9263443","GSM9263442","GSM9263441","GSM9263440","GSM9263439","GSM9263438","GSM9263437","GSM9263436"],"GPL":["19057"],"GSE":["309229"],"taxon":["Mus musculus"]}}