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

Published on Sep 1, 2019in Nature43.07
· DOI :10.1038/s41586-019-1485-8
Angel G. Solis3
Estimated H-index: 3
(Yale University),
Piotr Bielecki14
Estimated H-index: 14
(Yale University)
+ 13 AuthorsRichard A. Flavell7
Estimated H-index: 7
(Yale University)
Cite
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. PIEZO1 signalling mediates activation of a proinflammatory response to cyclical pressure fluctuations in immune cells.
  • References (40)
  • Citations (3)
Cite
References40
Newest
Published on Jun 19, 2019in Nature43.07
Will Bailis10
Estimated H-index: 10
(Yale University),
Justin A. Shyer2
Estimated H-index: 2
(Yale University)
+ 12 AuthorsRuaidhrí Jackson4
Estimated H-index: 4
(Yale University)
Activated CD4 T cells proliferate rapidly and remodel epigenetically before exiting the cell cycle and engaging acquired effector functions. Metabolic reprogramming from the naive state is required throughout these phases of activation1. In CD4 T cells, T-cell-receptor ligation—along with co-stimulatory and cytokine signals—induces a glycolytic anabolic program that is required for biomass generation, rapid proliferation and effector function2. CD4 T cell differentiation (proliferation and epige...
Published on Jan 1, 2019in Pulmonary circulation2.08
Ashley S. Lindsey4
Estimated H-index: 4
(USA: University of South Alabama),
Lydia M. Sullivan1
Estimated H-index: 1
(USA: University of South Alabama)
+ 4 AuthorsDiego F. Alvarez23
Estimated H-index: 23
(USA: University of South Alabama)
Herein we describe lung vascular injury and repair using a rodent model of Pseudomonas aeruginosa pneumonia-induced acute respiratory distress syndrome (ARDS) during: 1) the exudative phase (48-hou...
Published on Oct 10, 2018in Science Translational Medicine17.16
Swetha E. Murthy11
Estimated H-index: 11
(HHMI: Howard Hughes Medical Institute),
Meaghan Loud3
Estimated H-index: 3
(HHMI: Howard Hughes Medical Institute)
+ 8 AuthorsGary R. Lewin55
Estimated H-index: 55
(Charité)
The brush of a feather and a pinprick are perceived as distinct sensations because they are detected by discrete cutaneous sensory neurons. Inflammation or nerve injury can disrupt this sensory coding and result in maladaptive pain states, including mechanical allodynia, the development of pain in response to innocuous touch. However, the molecular mechanisms underlying the alteration of mechanical sensitization are poorly understood. In mice and humans, loss of mechanically activated PIEZO2 cha...
Published on Jul 31, 2017in Nature Reviews Immunology44.02
Morgan Huse19
Estimated H-index: 19
As leukocytes travel in the bloodstream, navigate through tissues and mediate effector functions, their behaviour is influenced by mechanical forces. In this Review, Morgan Huse explains how mechanical force regulates receptor activation, cell migration, intracellular signalling and intercellular communication.
Published on Nov 1, 2017in Cell Reports7.82
Jason Wu7
Estimated H-index: 7
(Duke University),
Michael Young1
Estimated H-index: 1
(Duke University)
+ 3 AuthorsJörg Grandl13
Estimated H-index: 13
(Duke University)
Summary Piezo proteins form mechanically activated ion channels that are responsible for our sense of light touch, proprioception, and vascular blood flow. Upon activation by mechanical stimuli, Piezo channels rapidly inactivate in a voltage-dependent manner through an unknown mechanism. Inactivation of Piezo channels is physiologically important, as it modulates overall mechanical sensitivity, gives rise to frequency filtering of repetitive mechanical stimuli, and is itself the target of numero...
Published on Oct 19, 2017in Blood16.56
Edyta Glogowska3
Estimated H-index: 3
(Yale University),
Eve R. Schneider8
Estimated H-index: 8
(Yale University)
+ 12 AuthorsAlison M. Freidmann1
Estimated H-index: 1
(Harvard University)
Mutations in PIEZO1 are the primary cause of hereditary xerocytosis, a clinically heterogeneous, dominantly inherited disorder of erythrocyte dehydration. We utilized next generation sequencing-based techniques to identify PIEZO1 mutations in individuals from 9 kindreds referred with suspected HX and/or undiagnosed congenital hemolytic anemia. Mutations were primarily found in the highly conserved, COOH-terminal pore region domain. Several mutations were novel and demonstrated ethnic specificity...
Published on Mar 1, 2017in Nature43.07
S. A. Gudipaty1
Estimated H-index: 1
(UofU: University of Utah),
J. Lindblom1
Estimated H-index: 1
(UofU: University of Utah)
+ 5 AuthorsJody Rosenblatt29
Estimated H-index: 29
The stretch-activated channel Piezo1 controls homeostatic epithelial cell numbers by activating cells to divide rapidly when under stretch strain from low density, and by activating cells to extrude and die when cells are under crowding strain.
Published on Dec 1, 2016in Trends in Biochemical Sciences16.89
Yuan He11
Estimated H-index: 11
(UM: University of Michigan),
Hideki Hara16
Estimated H-index: 16
(UM: University of Michigan),
Gabriel Núñez130
Estimated H-index: 130
(UM: University of Michigan)
Members of the nucleotide-binding domain and leucine-rich repeat (LRR)-containing (NLR) family and the pyrin and HIN domain (PYHIN) family can form multiprotein complexes termed ‘inflammasomes'. The biochemical function of inflammasomes is to activate caspase-1, which leads to the maturation of interleukin 1 beta (IL-1β) and IL-18 and the induction of pyroptosis, a form of cell death. Unlike other inflammasomes, the NLRP3 inflammasome can be activated by diverse stimuli. The importance of the NL...
Published on Dec 1, 2016in Journal of Clinical Investigation12.28
ShengPeng Wang7
Estimated H-index: 7
(MPG: Max Planck Society),
Ramesh Chennupati3
Estimated H-index: 3
(MPG: Max Planck Society)
+ 3 AuthorsStefan Offermanns73
Estimated H-index: 73
(MPG: Max Planck Society)
Published on Aug 22, 2016in Journal of Experimental Medicine10.89
Amanda Littlewood-Evans19
Estimated H-index: 19
(Novartis),
Sophie Sarret1
Estimated H-index: 1
(Novartis)
+ 12 AuthorsSaijel Patel1
Estimated H-index: 1
(Novartis)
When SUCNR1 /GPR91-expressing macrophages are activated by inflammatory signals, they change their metabolism and accumulate succinate. In this study, we show that during this activation, macrophages release succinate into the extracellular milieu. They simultaneously up-regulate GPR91, which functions as an autocrine and paracrine sensor for extracellular succinate to enhance IL-1β production. GPR91-deficient mice lack this metabolic sensor and show reduced macrophage activation and production ...
Cited By3
Newest
Published on Sep 4, 2019in Nature Reviews Immunology44.02
Lucy Bird L4
Estimated H-index: 4
A new study shows that monocytes, recruited to the lungs during an infection, sense alterations in physical forces and pressure and initiate a pro-inflammatory response. This environmental sensory axis is mediated by the mechanically activated calcium channel PIEZO1.
Published on Sep 19, 2019in Arteriosclerosis, Thrombosis, and Vascular Biology6.62
David J. Beech43
Estimated H-index: 43
(University of Leeds),
Antreas C. Kalli12
Estimated H-index: 12
(University of Leeds)
Mechanical forces are fundamental in cardiovascular biology, and deciphering the mechanisms by which they act remains a testing frontier in cardiovascular research. Here, we raise awareness of 2 re...
Published on Sep 10, 2019in Science Signaling6.48
Myeloid cells respond to mechanical force through the ion channel PIEZO1, which promotes their proinflammatory response.
Published on Sep 1, 2019in Nature43.07
Sarah R. Walmsley19
Estimated H-index: 19
Immune cells called monocytes enter the lung during infection. Whether they help to launch a defence response is affected by the pressure encountered there, which is sensed by an ion channel called PIEZO1. Activity of the PIEZO1 ion channel affects a defence response.