Laboratory for Skin Homeostasis, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
Nat Commun. 2024 May 15;15(1):4062. doi: 10.1038/s41467-024-48226-z.
The stratum corneum is the outermost skin layer with a vital role in skin barrier function. It is comprised of dead keratinocytes (corneocytes) and is known to maintain its thickness by shedding cells, although, the precise mechanisms that safeguard stratum corneum maturation and homeostasis remain unclear. Previous ex vivo studies have suggested a neutral-to-acidic pH gradient in the stratum corneum. Here, we use intravital pH imaging at single-corneocyte resolution to demonstrate that corneocytes actually undergo differentiation to develop three distinct zones in the stratum corneum, each with a distinct pH value. We identified a moderately acidic lower, an acidic middle, and a pH-neutral upper layer in the stratum corneum, with tight junctions playing a key role in their development. The upper pH neutral zone can adjust its pH according to the external environment and has a neutral pH under steady-state conditions owing to the influence of skin microbiota. The middle acidic pH zone provides a defensive barrier against pathogens. With mathematical modeling, we demonstrate the controlled protease activation of kallikrein-related peptidases on the stratum corneum surface that results in proper corneocyte shedding in desquamation. This work adds crucial information to our understanding of how stratum corneum homeostasis is maintained.
角质层是皮肤的最外层，在皮肤屏障功能中起着至关重要的作用。它由死亡的角朊细胞（角质细胞）组成，已知通过细胞脱落来维持其厚度，尽管维持角质层成熟和稳态的精确机制仍不清楚。先前的离体研究表明角质层中存在中性到酸性的 pH 梯度。在这里，我们使用单细胞分辨率的活体 pH 成像来证明角质细胞实际上在分化过程中会在角质层中形成三个不同的区域，每个区域都有不同的 pH 值。我们在角质层中确定了一个中等酸性的下层、一个酸性的中层和一个 pH 值中性的上层，紧密连接在它们的形成中起着关键作用。上层 pH 值中性区可以根据外部环境调节其 pH 值，并且由于皮肤微生物群的影响，在稳定状态下呈中性 pH 值。中层酸性 pH 值区为抵御病原体提供了一道防御屏障。通过数学建模，我们证明了激肽释放酶相关肽酶在角质层表面的受控蛋白酶激活，这导致在脱屑过程中适当的角质细胞脱落。这项工作为我们理解角质层稳态如何维持提供了重要信息。
