Research ArticleINNATE IMMUNITY

Targeting Piezo1 unleashes innate immunity against cancer and infectious disease

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Science Immunology  21 Aug 2020:
Vol. 5, Issue 50, eabb5168
DOI: 10.1126/sciimmunol.abb5168

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Myeloid cells feel the squeeze

The Piezo1 and Piezo2 proteins are excitatory ion channels used by mammalian cells to sense and respond to mechanical stimuli, but little is known about whether mechanosensors participate in immune responses. Aykut et al. investigated how modulation of Piezo1’s activity affects inflammation and immunity using agonist or antagonist compounds targeting Piezo1 along with mice lacking Piezo1 in myeloid cells. In isolated myeloid cells, Piezo1 served as the primary mechanosensory receptor. Loss of Piezo1 in myeloid cells or its global inhibition with a tarantula venom–derived peptide inhibited the differentiation of suppressive myeloid cells in mouse models of pancreatic adenocarcinoma and polymicrobial sepsis. These studies spotlight Piezo1-dependent mechanosensation as a checkpoint regulating differentiation of suppressive myeloid cells that stifle immune control of cancer and infection.

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