PIEZO1 mediates mechanical reprogramming of neutrophils for proangiogenic specialization in the lung
Jin Wang, Wenying Zhao, Wenjuan Bai, Dong Dong, Hui Wang, Xin Qi, Ajitha Thanabalasuriar, Youqiong Ye, Tian-le Xu, Hecheng Li, Paul Kubes, Bin Li, Jing Wang
Jin Wang, Wenying Zhao, Wenjuan Bai, Dong Dong, Hui Wang, Xin Qi, Ajitha Thanabalasuriar, Youqiong Ye, Tian-le Xu, Hecheng Li, Paul Kubes, Bin Li, Jing Wang
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Research Article Immunology Pulmonology Vascular biology

PIEZO1 mediates mechanical reprogramming of neutrophils for proangiogenic specialization in the lung

Abstract

Neutrophils are the most abundant immune cells that constantly patrol or marginate inside vascular beds to support immune homeostasis. The extent to which neutrophils undergo reprogramming in response to the changes in vascular architecture and the resultant biological implications of such adaptations remain unclear. Here, we performed intravital imaging and transcriptional profiling to investigate neutrophil behavior across different tissues. Our findings revealed that neutrophils had significant deformability and spontaneous calcium signaling while navigating through the narrow pulmonary vessels. Pulmonary neutrophils exhibited unique transcriptional profiles and were specialized for proangiogenic functions. We found that the mechanosensitive ion channel Piezo-type mechanosensitive ion channel component 1 (PIEZO1) was essential for neutrophil reprogramming. Deletion of Piezo1 in neutrophils ablated the lung-specific proangiogenic transcriptional signature and impaired capillary angiogenesis in both physiological and pathological conditions. Collectively, these data show that mechanical adaptation of neutrophils within the pulmonary vasculature drives their reprogramming in the lungs and promotes pulmonary vascular homeostasis.

Authors

Jin Wang, Wenying Zhao, Wenjuan Bai, Dong Dong, Hui Wang, Xin Qi, Ajitha Thanabalasuriar, Youqiong Ye, Tian-le Xu, Hecheng Li, Paul Kubes, Bin Li, Jing Wang

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Figure 1

Neutrophil behavior landscapes in different tissues.

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Neutrophil behavior landscapes in different tissues. (A) Schematic of ex...
(A) Schematic of experiment workflow. Parameters describing the motion and shape of hundreds of cells were extracted from intravital microscopy (IVM) imaging data analysis. A nonlinear reduction technique (UMAP) was performed to visualize the data in a low-dimensional space. (B and C) UMAP of behavioral traits of 2,500 neutrophils from liver, lung, and spleen. Each dot corresponds to a single cell, colored by sample origin (B) or cell type (C). (D) Heatmap showing the morphology and kinetics parameters for different neutrophil subsets. (E) Proportions of the 4 neutrophil clusters in 3 tissues. (F) Examples of neutrophil snapshots from intravital imaging for each cluster (left panel), their trajectory (middle panel), and their shapes (right panel). Scale bars: 15 μm. (G) Violin plots for the indicated parameters across the 4 behavioral groups; each dot corresponds to a single cell. Data were analyzed using a univariate multinomial model. Statistical significance was determined by 1-way ANOVA with Dunnett’s post hoc test.