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. 2021 Jan 25;4:114. doi: 10.1038/s42003-020-01618-5

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 9 — Schematic representation of the skin. Mammalian skin consists of the epidermis and dermis, separated by a basement membrane. The epidermis is a stratified squamous epithelium that is composed of several cell layers. Resting on the basement membrane is the basal layer, consisting of K14-expressing proliferating cells. The basal layer gives rise to differentiated cell layers of the K10-expressing spinous layer, filaggrin-expressing granular layer, and the stratum corneum. Under normal conditions, keratinocytes in the K14-positive basal layer proliferate EGFR-dependently. Chondroitin 6-sulfate prevents keratinocytes from over-proliferation by interacting with EGFR. In contrast, a decrease in chondroitin 6-sulfate enhances keratinocyte proliferation signaling via activation of EGFR and impairs epidermal barrier function. When environmental factors trigger psoriasis, normal keratinocytes can maintain homeostasis; therefore, psoriasis does not develop from a single stimulus. Downregulation of chondroitin 6-sulfates causes para-inflammation in keratinocytes and may render keratinocytes vulnerable to environmental factors. Thus, a decrease in chondroitin 6-sulfates caused by mutations in the C6st-1 or Fam20b genes may predispose individuals to psoriasis.