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These enzymes, like kallikreins (KLK), are responsible for the degradation of corneodesmosomes, the protein structures linking together corneocytes, and are regulated by Lympho\u2010Epithelial Kazal\u2010Type\u2010related Inhibitor (LEKTI). KLK activity increases at pH levels higher than physiological. An increase in skin surface pH has been observed in patients suffering from skin diseases characterized by impaired barrier function, like atopic dermatitis. In this work, we introduce an agent\u2010based model of the epidermis to study the impact of a change in skin surface pH on the structural and physiological properties of the epidermis, through the LEKTI\u2010KLK mechanism. We demonstrate that a less acidic pH, compared to the slightly acidic pH observed in healthy skin, is sufficient to significantly affect the water loss at the surface and the amount of irritant permeating through the epidermis. This weakening of the skin barrier function eventually results in a more intense skin inflammation following exposure to an external irritant. This work provides additional evidence that skin surface pH and serine proteases can be therapeutic targets to improve skin barrier integrity.<\/jats:p>","DOI":"10.1111\/exd.14698","type":"journal-article","created":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T13:47:16Z","timestamp":1667396836000},"page":"177-185","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Computational modelling predicts impaired barrier function and higher sensitivity to skin inflammation following pH elevation"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5812-3722","authenticated-orcid":false,"given":"El\u00e9a","family":"Thibault Greugny","sequence":"first","affiliation":[{"name":"Essential Health Translational Science, Johnson &amp; Johnson Sant\u00e9 Beaut\u00e9 France  Issy\u2010les\u2010Moulineaux France"},{"name":"Inria Saclay \u00cele\u2010de\u2010France, Lifeware Team  Palaiseau 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