Three stepwise pH progressions in stratum corneum for homeostatic maintenance of the skin

Keitaro Fukuda, Yoshihiro Ito, Yuki Furuichi, Takeshi Matsui, Hiroto Horikawa, Takuya Miyano, Takaharu Okada, Mark van Logtestijn, Reiko J. Tanaka, Atsushi Miyawaki, Masayuki Amagai

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number4062
JournalNature communications
Issue number1
Publication statusPublished - 2024 Dec

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General Physics and Astronomy


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