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Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity

Author

Listed:
  • Angel G. Solis

    (Yale University School of Medicine)

  • Piotr Bielecki

    (Yale University School of Medicine)

  • Holly R. Steach

    (Yale University School of Medicine)

  • Lokesh Sharma

    (Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine)

  • Christian C. D. Harman

    (Yale University School of Medicine)

  • Sanguk Yun

    (Yale University
    Yale University
    Yale University)

  • Marcel R. Zoete

    (Utrecht University)

  • James N. Warnock

    (University of Georgia)

  • S. D. Filip To

    (Mississippi State University)

  • Autumn G. York

    (Yale University School of Medicine)

  • Matthias Mack

    (University Hospital Regensburg)

  • Martin A. Schwartz

    (Yale University
    Yale University
    Yale University)

  • Charles. S. Cruz

    (Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine)

  • Noah W. Palm

    (Yale University School of Medicine)

  • Ruaidhrí Jackson

    (Yale University School of Medicine)

  • Richard A. Flavell

    (Yale University School of Medicine
    Yale University)

Abstract

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.

Suggested Citation

  • Angel G. Solis & Piotr Bielecki & Holly R. Steach & Lokesh Sharma & Christian C. D. Harman & Sanguk Yun & Marcel R. Zoete & James N. Warnock & S. D. Filip To & Autumn G. York & Matthias Mack & Martin , 2019. "Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity," Nature, Nature, vol. 573(7772), pages 69-74, September.
    • Handle: RePEc:nat:nature:v:573:y:2019:i:7772:d:10.1038_s41586-019-1485-8
    DOI: 10.1038/s41586-019-1485-8
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    Cited by:

    1. Haiqing Bai & Longlong Si & Amanda Jiang & Chaitra Belgur & Yunhao Zhai & Roberto Plebani & Crystal Yuri Oh & Melissa Rodas & Aditya Patil & Atiq Nurani & Sarah E. Gilpin & Rani K. Powers & Girija Goy, 2022. "Mechanical control of innate immune responses against viral infection revealed in a human lung alveolus chip," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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