G protein subunit Gγ13-mediated signaling pathway is critical to the inflammation resolution and functional recovery of severely injured lungs

Author:

Li Yi-Hong1,Yang Yi-Sen1,Xue Yan-Bo1,Lei Hao1,Zhang Sai-Sai1,Qian Junbin234,Yao Yushi5,Zhou Ruhong16ORCID,Huang Liquan167ORCID

Affiliation:

1. College of Life Sciences, Zhejiang University

2. Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women’s Hospital, Zhejiang University School of Medicine

3. Institute of Genetics, Zhejiang University School of Medicine

4. Cancer Center, Zhejiang University

5. Institute of Immunology and Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

6. Zhejiang University Shanghai Institute for Advanced Study

7. Monell Chemical Senses Center

Abstract

Tuft cells are a group of rare epithelial cells that can detect pathogenic microbes and parasites. Many of these cells express signaling proteins initially found in taste buds. It is, however, not well understood how these taste signaling proteins contribute to the response to the invading pathogens or to the recovery of injured tissues. In this study, we conditionally nullified the signaling G protein subunit Gγ13 and found that the number of ectopic tuft cells in the injured lung was reduced following the infection of the influenza virus H1N1. Furthermore, the infected mutant mice exhibited significantly larger areas of lung injury, increased macrophage infiltration, severer pulmonary epithelial leakage, augmented pyroptosis and cell death, greater bodyweight loss, slower recovery, worsened fibrosis and increased fatality. Our data demonstrate that the Gγ13-mediated signal transduction pathway is critical to tuft cells-mediated inflammation resolution and functional repair of the damaged lungs.To our best knowledge, it is the first report indicating subtype-specific contributions of tuft cells to the resolution and recovery.

Publisher

eLife Sciences Publications, Ltd

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