1. The chemokine receptor CXCR3 promotes CD8 + T cell-dependent lung pathology during influenza pathogenesis.
- Author
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Guo K, Yombo DJK, Wang Z, Navaeiseddighi Z, Xu J, Schmit T, Ahamad N, Tripathi J, De Kumar B, Mathur R, Hur J, Sun J, Olszewski MA, and Khan N
- Subjects
- Animals, Humans, Mice, CD8-Positive T-Lymphocytes, Lung, Mice, Inbred C57BL, Mice, Knockout, Receptors, Chemokine, Influenza, Human, Lung Injury
- Abstract
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 Cxcr3hi 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.- Published
- 2024
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