The dual role of CD8 T cells in influenza control and lung pathology is increasingly appreciated. To explore whether protective and pathological functions can be linked to specific subsets, we dissected CD8 T responses in influenza-infected murine lungs. Our single-cell RNA-sequencing (scRNA-seq) analysis revealed notable diversity in CD8 T subpopulations during peak viral load and infection-resolved state. While enrichment of a Cxcr3 CD8 T effector subset was associated with a more robust cytotoxic response, both CD8 T effector and central memory exhibited equally potent effector potential. The scRNA-seq analysis identified unique regulons regulating the cytotoxic response in CD8 T cells. The late-stage CD8 T blockade in influenza-cleared lungs or continuous CXCR3 blockade mitigated lung injury without affecting viral clearance. Furthermore, adoptive transfer of wild-type CD8 T cells exacerbated influenza lung pathology in Cxcr3 mice. Collectively, our data imply that CXCR3 interception could have a therapeutic effect in preventing influenza-linked lung injury.
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http://dx.doi.org/10.1126/sciadv.adj1120 | DOI Listing |
Virol J
January 2025
Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, People's Republic of China.
Monkeypox virus (MPXV) is an important zoonotic pathogenic virus, which poses serious threats to public health. MPXV infection can be prevented by immunization against the variola virus. Because of the safety risks and side effects of vaccination with live vaccinia virus (VACV) strain Tian Tan (VTT), we constructed two gene-deleted VTT recombinants (TTVAC7 and TTVC5).
View Article and Find Full Text PDFSci Rep
January 2025
Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
An ideal chemotherapeutic agent damages DNA, specifically in cancer cells, without harming normal cells. Recently, we used Box A of HMGB1 plasmid as molecular scissors to produce DNA gaps in normal cells. The DNA gap relieves DNA tension and increases DNA strength, preventing DNA double-strand breaks (DSBs).
View Article and Find Full Text PDFZhonghua Bing Li Xue Za Zhi
February 2025
Department of Pathology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, China.
Clin Lung Cancer
January 2025
Thoracic Surgery Unit, IRCCS National Cancer Institute Regina Elena, Rome, Italy.
Introduction: To analyze the impact of Kirsten-Rat-Sarcoma Virus (KRAS) mutations on tumor-growth as estimated by tumor-doubling-time (TDT) among solid-dominant clinical-stage I lung adenocarcinoma. Moreover, to evaluate the prognostic role of KRAS mutations, TDT and their combination in completely-resected pathologic-stage I adenocarcinomas.
Methods: In this single-center retrospective analysis, completely resected clinical-stage I adenocarcinomas presenting as solid-dominant nodules (consolidation-to-tumor ratio > 0.
Methods Cell Biol
January 2025
Laboratory of Translational Oncology, Program in Solid Tumors, Cima Universidad de Navarra, Cancer Center Clínica Universidad de Navarra (CCUN), Pamplona, Spain; Department of Biochemistry and Genetics, School of Sciences, Universidad de Navarra, Pamplona, Spain; Navarra's Health Research Institute (IDISNA), Pamplona, Spain; Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain. Electronic address:
Combined blockade of the immune checkpoints PD-1 and CTLA-4 has shown remarkable efficacy in patients with melanoma, renal cell carcinoma, non-small-cell lung cancer and mesothelioma, among other tumor types. However, a proportion of patients suffer from serious immune-related adverse events (irAEs). In severe cases, a reduction of the doses or the complete cessation of the treatment is required, limiting the antitumor efficacy of these treatments.
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