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, Ca(2+) 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–β (TGFβ) 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.