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_H1) and T_H17 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.