Piezo mechanosensitive channels: A biological hub for intestinal barrier homeostasis and an emerging target for disease intervention

Figure 3 Piezo regulates immune responses by coordinating dendritic cells, natural killer cells, and enterochromaffin cells. A: Piezo1 drives the activation of the calcium-dependent calcineurin-nuclear factor of activated T-cells pathway, activates the sirtuin 1-hypoxia-inducible factor 1-alpha axis to enhance glycolytic gene expression, promotes interleukin-12 production to amplify T helper type 1 cells, downregulates transforming growth factor β1 to inhibit regulatory T cell differentiation, and, in collaboration with the Hippo pathway effectors transcriptional co-activator with PDZ-binding motif/yes-associated protein, directly upregulates key glycolytic genes, thereby enhancing the innate immune phenotype of dendritic cells; B: Piezo1 reduces the killing efficiency of natural killer cells during tumor cell softening and shortens the killing time of natural killer cells during tumor cell hardening; C: Enterochromaffin cells sense mechanical forces through the Piezo2 channel. When Piezo2 is activated, it releases 5-hydroxytryptamine, which further activates enteric neurons, promotes intestinal fluid secretion, and maintains the oscillation of the transcription factor hairy and enhancer of split 1 through calcium signaling, thereby inhibiting intestinal inflammation. DCs: Dendritic cells; C-NFAT: Calcineurin nuclear factor of activated T-cells; TAZ: Transcriptional co-activator with PDZ-binding motif; YAP: Yes-associated protein; SIRT1: Sirtuin 1; HIF-1α: Hypoxia-inducible factor 1-alpha; IL-12: Interleukin 12; TGF-β1: Transforming growth factor β1; Th1: T helper type 1; Treg: Regulatory T cell; NK cells: Natural killer cells; ECs: Enterochromaffin cells; 5-HT: 5-hydroxytryptamine; Hes1: Hairy and enhancer of split 1.