Piezo1 Channels Restrain Regulatory T Cells But Are Dispensable For Effector Cd4(+) T Cell Responses

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 (T(H)1) and T(H)17 subsets. However, Piezo1 deletion in T cells resulted in enhanced transforming growth factor-beta (TGF beta) signaling and an expanded pool of regulatory T (T-reg) cells. Moreover, mice with deletion of Piezo1 specifically in T-reg cells showed significant attenuation of EAE. Our results indicate that Piezo1 selectively restrains T-reg cells, without influencing activation events or effector T cell functions.