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Cell Death Dis. 2018 Mar 6;9(3):369. doi: 10.1038/s41419-018-0412-5.

Group 2 innate lymphoid cells protect lung endothelial cells from pyroptosis in sepsis.

Lai D1,2, Tang J2,3, Chen L2,4, Fan EK5, Scott MJ2, Li Y2,6, Billiar TR2,7, Wilson MA2,6, Fang X8, Shu Q9, Fan J10,11,12.

Author information

1
Department of Thoracic and Cardiovascular Surgery, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
2
Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
3
Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
4
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
5
University of Pittsburgh School of Arts and Science, Pittsburgh, PA, USA.
6
Research and Development, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA, USA.
7
McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
8
Department of Anesthesiology and Intensive Care Unit, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. xmfang@zju.edu.cn.
9
Department of Thoracic and Cardiovascular Surgery, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. shuqiang@zju.edu.cn.
10
Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. jif7@pitt.edu.
11
Research and Development, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA, USA. jif7@pitt.edu.
12
McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA. jif7@pitt.edu.

Abstract

Group 2 innate lymphoid cells (ILC2) are one of three subgroups of innate lymphoid cells (ILC1, ILC2, and ILC3), and the major ILC population detected in the lungs. The function of ILC2 in the regulation of lung inflammation remains unclear. In the current study, we explored an important role of ILC2 in protecting lung endothelial cell (EC) from pyroptosis in sepsis-induced acute lung inflammation and the underlying mechanism. Using a cecal ligation and puncture (CLP) mouse sepsis model, we demonstrated that IL-33, which is released in response to sepsis, acting through its receptor ST2 mediates ILC2 expansion in the lungs. We further showed that the increased ILC2 in the lungs secrete IL-9, which in turn prevents lung EC from undergoing pyroptosis, a pro-inflammatory cell death form, by attenuating caspase-1 activation. These findings suggest a previously unidentified innate pathway that negatively regulates lung inflammation following sepsis.

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