Piezo1 channels restrain regulatory T cells but are dispensable for effector CD4+ T cell responses

Sci Adv. 2021 Jul 7;7(28):eabg5859. doi: 10.1126/sciadv.abg5859. Print 2021 Jul.


T lymphocytes encounter complex mechanical cues during an immune response. The mechanosensitive ion channel, Piezo1, drives inflammatory responses to bacterial infections, wound healing, and cancer; however, its role in helper T cell function remains unclear. In an animal model for multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), we found that mice with genetic deletion of Piezo1 in T cells showed diminished disease severity. Unexpectedly, Piezo1 was not essential for lymph node homing, interstitial motility, Ca2+ signaling, T cell proliferation, or differentiation into proinflammatory T helper 1 (TH1) and TH17 subsets. However, Piezo1 deletion in T cells resulted in enhanced transforming growth factor-β (TGFβ) signaling and an expanded pool of regulatory T (Treg) cells. Moreover, mice with deletion of Piezo1 specifically in Treg cells showed significant attenuation of EAE. Our results indicate that Piezo1 selectively restrains Treg cells, without influencing activation events or effector T cell functions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Encephalomyelitis, Autoimmune, Experimental* / pathology
  • Ion Channels / genetics
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Multiple Sclerosis*
  • T-Lymphocytes, Regulatory
  • Th1 Cells


  • Ion Channels
  • Piezo1 protein, mouse