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Gut-derived memory γδ T17 cells exacerbate sepsis-induced acute lung injury in mice.
- Source :
-
Nature communications [Nat Commun] 2024 Aug 07; Vol. 15 (1), pp. 6737. Date of Electronic Publication: 2024 Aug 07. - Publication Year :
- 2024
-
Abstract
- Sepsis is a critical global health concern linked to high mortality rates, often due to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). While the gut-lung axis involvement in ALI is recognized, direct migration of gut immune cells to the lung remains unclear. Our study reveals sepsis-induced migration of γδ T17 cells from the small intestine to the lung, triggering an IL-17A-dominated inflammatory response in mice. Wnt signaling activation in alveolar macrophages drives CCL1 upregulation, facilitating γδ T17 cell migration. CD44 <superscript>+</superscript> Ly6C <superscript>-</superscript> IL-7R <superscript>high</superscript> CD8 <superscript>low</superscript> cells are the primary migratory subtype exacerbating ALI. Esketamine attenuates ALI by inhibiting pulmonary Wnt/β-catenin signaling-mediated migration. This work underscores the pivotal role of direct gut-to-lung memory γδ T17 cell migration in septic ALI and clarifies the importance of localized IL-17A elevation in the lung.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Mice
Male
Receptors, Antigen, T-Cell, gamma-delta metabolism
Wnt Signaling Pathway immunology
Macrophages, Alveolar immunology
Intestine, Small immunology
Intestine, Small pathology
Intraepithelial Lymphocytes immunology
Disease Models, Animal
Antigens, Ly metabolism
Immunologic Memory
Sepsis immunology
Sepsis complications
Acute Lung Injury immunology
Acute Lung Injury pathology
Interleukin-17 metabolism
Interleukin-17 immunology
Cell Movement
Lung immunology
Lung pathology
Mice, Inbred C57BL
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 39112475
- Full Text :
- https://doi.org/10.1038/s41467-024-51209-9