Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE

Publication: Basingstoke : Nature Publishing Group
Original Publication: London, Macmillan Journals ltd.

Hydrostatic Pressure* ; Immunity, Innate*; Ion Channels/*metabolism ; Mechanotransduction, Cellular/*immunology; Animals ; Endothelin-1/metabolism ; Female ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Inflammation/immunology ; Inflammation/metabolism ; Inflammation/microbiology ; JNK Mitogen-Activated Protein Kinases/metabolism ; Lung/immunology ; Lung/metabolism ; Lung/microbiology ; Macrophages/immunology ; Macrophages/metabolism ; Male ; Mice ; Pseudomonas Infections/immunology ; Pseudomonas aeruginosa/immunology ; Signal Transduction

Direct recognition of invading pathogens by innate immune cells is a critical driver of the inflammatory response. However, cells of the innate immune system can also sense their local microenvironment and respond to physiological fluctuations in temperature, pH, oxygen and nutrient availability, which are altered during inflammation. Although cells of the immune system experience force and pressure throughout their life cycle, little is known about how these mechanical processes regulate the immune response. Here we show that cyclical hydrostatic pressure, similar to that experienced by immune cells in the lung, initiates an inflammatory response via the mechanically activated ion channel PIEZO1. Mice lacking PIEZO1 in innate immune cells showed ablated pulmonary inflammation in the context of bacterial infection or fibrotic autoinflammation. Our results reveal an environmental sensory axis that stimulates innate immune cells to mount an inflammatory response, and demonstrate a physiological role for PIEZO1 and mechanosensation in immunity.

Comment in: Nature. 2019 Sep;573(7772):41-42. (PMID: 31481766)
Comment in: Nat Rev Immunol. 2019 Oct;19(10):595. (PMID: 31485035)
Erratum in: Nature. 2019 Nov 12;:. (PMID: 31712625)

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R01 GM122984 United States GM NIGMS NIH HHS; R01 HL075092 United States HL NHLBI NIH HHS; T32 GM007499 United States GM NIGMS NIH HHS; UL1 TR001863 United States TR NCATS NIH HHS

0 (Endothelin-1)
0 (Hif1a protein, mouse)
0 (Hypoxia-Inducible Factor 1, alpha Subunit)
0 (Ion Channels)
0 (Piezo1 protein, mouse)
EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)

Date Created: 20190823 Date Completed: 20200330 Latest Revision: 20220417

20231215

PMC6939392

10.1038/s41586-019-1485-8

31435009