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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.
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http://dx.doi.org/10.1172/JCI183796 | DOI Listing |
BMB Rep
September 2025
Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea; Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea; Institute for Immunology and Immunological Diseases, Yonsei Uni
B cell tolerance is critical for preventing autoimmunity, yet the mechanisms by which B cells discriminate self from non-self antigens remain incompletely understood. While early findings emphasize the role of classical antigen-mediated BCR signaling strength by varying antigen formats, emerging evidence highlights the importance of mechanical cues during antigen recognition. This review explores how mechanosensitive ion channels, particularly Piezo1, contribute to B cell activation and tolerance by integrating physical forces at the immune synapse.
View Article and Find Full Text PDFBioessays
September 2025
Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
Neutrophil extracellular traps (NETs)-web-like DNA structures extruded by neutrophils in response to various stimuli, including pathogens, sterile inflammation, and mechanical stress-play a dual role in immunity and disease. While NETs serve to trap and neutralize pathogens during host defense, excessive or dysregulated NET formation, known as NETosis, can amplify inflammation and contribute to thrombotic complications such as atherosclerosis and valve disease. Increasing evidence supports that NETosis is a regulated, signaling-driven process, and that mechanical forces-including shear stress, tensile force, and matrix stiffness-can act as noncanonical danger signals capable of inducing NETosis.
View Article and Find Full Text PDFAdv Sci (Weinh)
September 2025
Department of Otolaryngology-Head and Neck Surgery, Stanford University, Palo Alto, 94304, USA.
The plasma membrane is actively regulated by lipid transporters that create electrochemical gradients between leaflets, and passively by scramblases that dissipate these gradients. Membrane properties such as lipid packing are critical for the proper function of transmembrane proteins, particularly mechanosensitive ion channels. Mechanosensation is a key component of many sensory processes including balance, and hearing.
View Article and Find Full Text PDFMol Biol Rep
September 2025
School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, 301600, Tianjin, China.
Piezo1, a mechanosensitive cation channel characterized by its distinctive transmembrane trimeric structure, plays a pivotal role in mediating cellular responses to mechanical stimuli. It facilitates calcium influx, and recent studies highlight its involvement in heart failure (HF) pathophysiology, where its dysregulation significantly contributes to disease progression. Specifically, Piezo1 upregulation impacts diverse cellular processes across cardiovascular cell types, including cardiomyocytes, fibroblasts, endothelial cells (ECs), and vascular smooth muscle cells (VSMCs).
View Article and Find Full Text PDFNat Biomed Eng
September 2025
Developmental, Stem Cell and Cancer Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
Biofluid flow generates fluid shear stress (FSS), a mechanical force widely present in the tissue microenvironment. How brain tumour growth alters the conduit of biofluid and impacts FSS-regulated cancer progression is unknown. Dissemination of medulloblastoma (MB) cells into the cerebrospinal fluid initiates metastasis within the central nervous system.
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