Human β-defensin-3 (hBD-3) exhibits antimicrobial and immunomodulatory activities; however, its contribution to autophagy regulation remains unclear, and the role of autophagy in the regulation of the epidermal barrier in atopic dermatitis (AD) is poorly understood. Here, keratinocyte autophagy was restrained in the skin lesions of patients with AD and murine models of AD. Interestingly, hBD-3 alleviated the IL-4– and IL-13–mediated impairment of the tight junction (TJ) barrier through keratinocyte autophagy activation, which involved aryl hydrocarbon receptor (AhR) signaling. While autophagy deficiency impaired the epidermal barrier and exacerbated inflammation, hBD-3 attenuated skin inflammation and enhanced the TJ barrier in AD. Importantly, hBD-3–mediated improvement of the TJ barrier was abolished in autophagy-deficient AD mice and in AhR-suppressed AD mice, suggesting a role for hBD-3–mediated autophagy in the regulation of the epidermal barrier and inflammation in AD. Thus, autophagy contributes to the pathogenesis of AD, and hBD-3 could be used for therapeutic purposes.

中文翻译：

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人 β-defensin-3 通过自噬激活和芳烃受体信号通路减轻特应性皮炎样炎症

人 β-defensin-3 (hBD-3) 具有抗菌和免疫调节活性；然而，其对自噬调节的贡献仍不清楚，自噬在特应性皮炎（AD）表皮屏障调节中的作用也知之甚少。在这里，角质形成细胞自噬在 AD 患者和 AD 小鼠模型的皮肤病变中受到抑制。有趣的是，hBD-3 通过角质形成细胞自噬激活减轻了 IL-4 和 IL-13 介导的紧密连接 (TJ) 屏障损伤，这涉及芳烃受体 (AhR) 信号传导。虽然自噬缺乏会损害表皮屏障并加剧炎症，但 hBD-3 可减轻皮肤炎症并增强 AD 中的 TJ 屏障。重要的，hBD-3 介导的 TJ 屏障改善在自噬缺陷型 AD 小鼠和 AhR 抑制的 AD 小鼠中被消除，这表明 hBD-3 介导的自噬在调节表皮屏障和 AD 炎症中的作用。因此，自噬有助于 AD 的发病机制，并且 hBD-3 可用于治疗目的。