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

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

Nat Commun. 2024 Aug 7;15(1):6737. doi: 10.1038/s41467-024-51209-9.

Authors

Bing Xie^#^{1

2}, Mengyuan Wang^#^{1

2}, Xinyu Zhang^#^{1

2}, Yujing Zhang^#^{1

2}, Hong Qi^#^{1

2}, Hong Liu^{1

2}, Yuming Wu^{1

2}, Xiaoyue Wen^{1

2}, Xiaoyan Chen^{1

2}, Mengqi Han^{1

2}, Dan Xu^{1

2}, Xueqiang Sun^{1

2}, Xue Zhang^{1

2}, Xin Zhao^{1

2}, You Shang^{3

4}, Shiying Yuan^{5

6}, Jiancheng Zhang^{7

8}

Affiliations

¹ Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
² Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
³ Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China. shang_you@126.com.
⁴ Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China. shang_you@126.com.
⁵ Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China. yuan_shiying@163.com.
⁶ Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China. yuan_shiying@163.com.
⁷ Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China. zhjcheng1@126.com.
⁸ Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China. zhjcheng1@126.com.

^# Contributed equally.

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-7R^high CD8^low 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.

MeSH terms

Acute Lung Injury* / immunology
Acute Lung Injury* / pathology
Animals
Antigens, Ly / metabolism
Cell Movement*
Disease Models, Animal
Immunologic Memory
Interleukin-17* / immunology
Interleukin-17* / metabolism
Intestine, Small / immunology
Intestine, Small / pathology
Intraepithelial Lymphocytes / immunology
Lung* / immunology
Lung* / pathology
Macrophages, Alveolar / immunology
Male
Mice
Mice, Inbred C57BL*
Receptors, Antigen, T-Cell, gamma-delta / metabolism
Sepsis* / complications
Sepsis* / immunology
Wnt Signaling Pathway / immunology

Substances

Interleukin-17
Receptors, Antigen, T-Cell, gamma-delta
Il17a protein, mouse
Antigens, Ly

Abstract

MeSH terms

Substances

Grants and funding