Gut-derived memory γδ T17 cells exacerbate sepsis-induced acute lung injury in mice

Bing Xie; Mengyuan Wang; Xinyu Zhang; Yujing Zhang; Hong Qi; Hong Liu; Yuming Wu; Xiaoyue Wen; Xiaoyan Chen; Mengqi Han; Dan Xu; Xueqiang Sun; Xue Zhang; Xin Zhao; You Shang; Shiying Yuan; Jiancheng Zhang

doi:10.1038/s41467-024-51209-9

Nature Communications (Aug 2024)

Gut-derived memory γδ T17 cells exacerbate sepsis-induced acute lung injury in mice

Bing Xie,
Mengyuan Wang,
Xinyu Zhang,
Yujing Zhang,
Hong Qi,
Hong Liu,
Yuming Wu,
Xiaoyue Wen,
Xiaoyan Chen,
Mengqi Han,
Dan Xu,
Xueqiang Sun,
Xue Zhang,
Xin Zhao,
You Shang,
Shiying Yuan,
Jiancheng Zhang

Affiliations

Bing Xie: Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Mengyuan Wang: Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Xinyu Zhang: Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Yujing Zhang: Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Hong Qi: Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Hong Liu: Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Yuming Wu: Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Xiaoyue Wen: Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Xiaoyan Chen: Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Mengqi Han: Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Dan Xu: Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Xueqiang Sun: Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Xue Zhang: Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Xin Zhao: Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
You Shang: Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Shiying Yuan: Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Jiancheng Zhang: Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

DOI: https://doi.org/10.1038/s41467-024-51209-9
Journal volume & issue: Vol. 15, no. 1
pp. 1 – 16

Abstract

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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+ Ly6C– IL-7Rhigh CD8low 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.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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