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Changes in the skin mycobiome have been observed in this disease, specifically\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>Candida albicans<\/jats:italic>\n                      <\/jats:styled-content>\n                      colonization positively correlating with AD severity, yet the mechanisms by which this fungus contributes to disease features remain elusive.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      This study aimed to elucidate how\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>C. albicans<\/jats:italic>\n                      <\/jats:styled-content>\n                      can influence AD pathogenesis through its influence on keratinocyte (KC) proteolytic activity, inflammatory cytokine secretion and epidermal barrier integrity, as well as define the signaling pathways mediating these effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Immortalized human KC were co\u2010cultured with\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>C. albicans<\/jats:italic>\n                      <\/jats:styled-content>\n                      and changes in KC protease expression and activity, along with the secretion of the pro\u2010inflammatory cytokine IL\u20101\u03b2 were assessed. Additionally, the impact of IL\u20101\u03b2 on KC barrier formation was determined using transepithelial electrical resistance. To identify signalling pathways mediating\n                      <jats:italic>Candida<\/jats:italic>\n                      \u2010induced phenotypes, CRISPR\/Cas9 was used to establish cell lines deficient in myeloid differentiation primary response protein 88 (MyD88) or matrix metalloprotease\u20109 (MMP\u20109).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>C. albicans<\/jats:italic>\n                      <\/jats:styled-content>\n                      induced proteolytic activity from KC through fungal secreted aspartyl proteases (Sap4\u20106) and promoted IL\u20101\u03b2 secretion via MyD88 signalling. This response increased expression and activation of host MMP\u20109 and led to impaired barrier function. Genetic deletion of either\n                      <jats:italic>MYD88<\/jats:italic>\n                      or\n                      <jats:italic>MMP9<\/jats:italic>\n                      restored barrier function in IL\u20101\u03b2 treated cells, suggesting MMP\u20109 serves as a downstream effector of IL\u20101\u03b2\/MyD88 signalling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These findings establish a mechanistic link between skin resident fungi and epidermal barrier dysfunction. We demonstrate a pathway linking fungal colonization to innate immune responses by skin cells, providing insight into how the commensal fungus\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>C. albicans<\/jats:italic>\n                      <\/jats:styled-content>\n                      may contribute to AD pathogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/myc.70133","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T14:16:16Z","timestamp":1764166576000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>\n                      <i>Candida albicans<\/i>\n                    <\/scp>\n                    Enhances Protease Activity and Activates\n                    <scp>MyD88<\/scp>\n                    \u2010Dependent\n                    <scp>IL<\/scp>\n                    \u20101\u03b2 Production in Human Keratinocytes"],"prefix":"10.1111","volume":"68","author":[{"given":"Jingyi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Dermatology University of Rochester  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil A. 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