Dynamic keratinocyte Piezo2 expression drives itch and nerve remodeling in atopic dermatitis
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PUBLIC SUMMARY
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Keratinocyte Piezo2 is selectively upregulated in AD.
Piezo2-Sema3a axis drives itch and nerve remodeling.
Piezo2 is involved in AD itch.
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ABSTRACT
Keratinocytes actively contribute to somatosensory signaling in chronic skin diseases, yet the mechanotransduction mechanisms involved in atopic dermatitis (AD)-associated itch remain unclear. Here we identify keratinocyte-expressed mechanosensitive ion channel Piezo2 as a critical driver of chronic itch in AD. While Piezo1 was constitutively expressed and dispensable for chronic itch in the MC903-induced AD model, Piezo2 expression was markedly upregulated in keratinocytes of lesional AD skin. Keratinocyte-specific Piezo2 deletion attenuated spontaneous scratching and spontaneous C fiber activity, while having minimal impact on skin inflammation. Mechanistically, Piezo2 suppressed the neurorepulsive factor Semaphorin 3A (Sema3a), a key regulator of sensory nerve architecture. Loss of Piezo2 restored Sema3a expression in the epidermis, reduced nerve fiber branching, and dampened C fiber hyperexcitability. Furthermore, keratinocyte-specific ablation of Sema3a exacerbated AD-related itch and nerve fiber outgrowth. These findings establish a non-neuronal epithelial mechanism wherein keratinocyte Piezo2 modulates sensory nerve remodeling and pruritus in chronic skin inflammation, offering potential targets for therapeutic intervention. -
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REFERENCES
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Hu X., Wu L., Zhao G., et al. (2026). Dynamic keratinocyte Piezo2 expression drives itch and nerve remodeling in atopic dermatitis. The Innovation Life 4:100187. https://doi.org/10.59717/j.xinn-life.2026.100187
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Hu X., Wu L., Zhao G., et al. (2026). Dynamic keratinocyte Piezo2 expression drives itch and nerve remodeling in atopic dermatitis. The Innovation Life 4:100187. https://doi.org/10.59717/j.xinn-life.2026.100187
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Figure 1.
Keratinocyte Piezo2 expression is upregulated in AD-like skin and drives chronic itch
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Figure 2.
Keratinocyte-expressed Piezo2 promotes epidermal sensory fiber remodeling, but does not affect skin inflammation in MC903-induced AD
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Figure 3.
Keratinocyte-expressed Piezo2 enhances C fiber excitability during AD-associated itch
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Figure 4.
PIEZO2 is required for suppressing Sema3a expression in the context of AD
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Figure 5.
Keratinocyte Sema3a is essential for AD-associated chronic itch
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Figure 6.
Piezo2-Sema3a signaling is essential for AD-associated chronic itch
