Three Stepwise PH Progressions in Stratum Corneum for Homeostatic Maintenance of the Skin

Overview

Journal Nat Commun

Specialty Biology

Date 2024 May 15

PMID 38750035

Authors

Keitaro Fukuda

Yoshihiro Ito

Yuki Furuichi

Takeshi Matsui

Hiroto Horikawa

Takuya Miyano

Takaharu Okada

Mark van Logtestijn

Reiko J Tanaka

Atsushi Miyawaki

Masayuki Amagai

Affiliations

Soon will be listed here.

Abstract

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.

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