tetano
Editor, Senior Moderator
Sci Adv
. 2024 Jan 5;10(1):eadj1120.
doi: 10.1126/sciadv.adj1120. Epub 2024 Jan 3. The chemokine receptor CXCR3 promotes CD8[SUP]+[/SUP] T cell-dependent lung pathology during influenza pathogenesis
Kai Guo[SUP] 1 [/SUP], Dan J K Yombo[SUP] 2 [/SUP], Zhihan Wang[SUP] 2 3 [/SUP], Zahrasadat Navaeiseddighi[SUP] 4 [/SUP], Jintao Xu[SUP] 5 6 [/SUP], Taylor Schmit[SUP] 2 [/SUP], Nassem Ahamad[SUP] 4 [/SUP], Jitendra Tripathi[SUP] 2 [/SUP], Bony De Kumar[SUP] 2 [/SUP], Ramkumar Mathur[SUP] 7 [/SUP], Junguk Hur[SUP] 2 [/SUP], Jie Sun[SUP] 8 9 [/SUP], Michal A Olszewski[SUP] 5 6 [/SUP], Nadeem Khan[SUP] 2 4 [/SUP]
Affiliations
The dual role of CD8[SUP]+[/SUP] 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[SUP]+[/SUP] T responses in influenza-infected murine lungs. Our single-cell RNA-sequencing (scRNA-seq) analysis revealed notable diversity in CD8[SUP]+[/SUP] T subpopulations during peak viral load and infection-resolved state. While enrichment of a Cxcr3[SUP]hi[/SUP] CD8[SUP]+[/SUP] T effector subset was associated with a more robust cytotoxic response, both CD8[SUP]+[/SUP] T effector and central memory exhibited equally potent effector potential. The scRNA-seq analysis identified unique regulons regulating the cytotoxic response in CD8[SUP]+[/SUP] T cells. The late-stage CD8[SUP]+[/SUP] T blockade in influenza-cleared lungs or continuous CXCR3 blockade mitigated lung injury without affecting viral clearance. Furthermore, adoptive transfer of wild-type CD8[SUP]+[/SUP] T cells exacerbated influenza lung pathology in Cxcr3[SUP]-/-[/SUP] mice. Collectively, our data imply that CXCR3 interception could have a therapeutic effect in preventing influenza-linked lung injury.
. 2024 Jan 5;10(1):eadj1120.
doi: 10.1126/sciadv.adj1120. Epub 2024 Jan 3. The chemokine receptor CXCR3 promotes CD8[SUP]+[/SUP] T cell-dependent lung pathology during influenza pathogenesis
Kai Guo[SUP] 1 [/SUP], Dan J K Yombo[SUP] 2 [/SUP], Zhihan Wang[SUP] 2 3 [/SUP], Zahrasadat Navaeiseddighi[SUP] 4 [/SUP], Jintao Xu[SUP] 5 6 [/SUP], Taylor Schmit[SUP] 2 [/SUP], Nassem Ahamad[SUP] 4 [/SUP], Jitendra Tripathi[SUP] 2 [/SUP], Bony De Kumar[SUP] 2 [/SUP], Ramkumar Mathur[SUP] 7 [/SUP], Junguk Hur[SUP] 2 [/SUP], Jie Sun[SUP] 8 9 [/SUP], Michal A Olszewski[SUP] 5 6 [/SUP], Nadeem Khan[SUP] 2 4 [/SUP]
Affiliations
- PMID: 38170765
- DOI: 10.1126/sciadv.adj1120
The dual role of CD8[SUP]+[/SUP] 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[SUP]+[/SUP] T responses in influenza-infected murine lungs. Our single-cell RNA-sequencing (scRNA-seq) analysis revealed notable diversity in CD8[SUP]+[/SUP] T subpopulations during peak viral load and infection-resolved state. While enrichment of a Cxcr3[SUP]hi[/SUP] CD8[SUP]+[/SUP] T effector subset was associated with a more robust cytotoxic response, both CD8[SUP]+[/SUP] T effector and central memory exhibited equally potent effector potential. The scRNA-seq analysis identified unique regulons regulating the cytotoxic response in CD8[SUP]+[/SUP] T cells. The late-stage CD8[SUP]+[/SUP] T blockade in influenza-cleared lungs or continuous CXCR3 blockade mitigated lung injury without affecting viral clearance. Furthermore, adoptive transfer of wild-type CD8[SUP]+[/SUP] T cells exacerbated influenza lung pathology in Cxcr3[SUP]-/-[/SUP] mice. Collectively, our data imply that CXCR3 interception could have a therapeutic effect in preventing influenza-linked lung injury.