{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:07:30Z","timestamp":1790712450413,"version":"4.1.0"},"reference-count":91,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Psoriasis is a chronic immune-mediated inflammatory disorder characterized by epidermal hyperplasia, barrier dysfunction, and dysregulated crosstalk between keratinocytes and adaptive immune cells. Although the IL-23\/IL-17 axis remains central to disease pathogenesis, the extracellular mechanisms that sustain and amplify inflammation are not well defined. Emerging evidence highlights extracellular proteolysis as a critical regulator of inflammatory persistence in psoriatic skin by modulating cytokine bioavailability, receptor activation, extracellular matrix remodeling, and immune cell trafficking, including the release of angiogenic mediators such as VEGF. Zinc-dependent metalloproteases are key contributors to these processes. Among them, meprin \u03b1 and meprin \u03b2 exhibit distinct structural and spatial characteristics, positioning them as context-dependent regulators of epithelial and immune homeostasis. In psoriatic lesions, meprin \u03b1 overexpression results in keratinocyte hyperproliferation, barrier deficiencies with increased transepidermal water loss, and local inflammation due to the proteolytic cleavage of dermokine, an essential regulator of immune responses and epidermal differentiation. Additionally, it is mislocalized to the suprabasal layers. Meprin-\u03b1 has also been shown to synchronize the activation of skin barrier proteins, effectively contributing to sustained barrier integrity. This, together with the pathogenic repercussions of the meprin-driven pro-inflammatory milieu, has far-reaching implications for this understudied protein. Thus, the current review synthesizes evidence implicating meprins in keratinocyte differentiation, barrier integrity, cytokine processing, and matrix remodeling. We further discuss the regulatory mechanisms that control meprin expression and evaluate its therapeutic potential as an upstream modulator of extracellular inflammatory signaling in psoriasis.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1817338","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:54:03Z","timestamp":1783490043000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Meprin proteases in cutaneous homeostasis and psoriasis: pathophysiological mechanisms and therapeutic prospects"],"prefix":"10.3389","volume":"17","author":[{"given":"Vineetkumar","family":"Pillai","sequence":"first","affiliation":[{"name":"Immunopathology Lab, School of Biosciences and Technology, Vellore Institute of Technology (VIT)","place":["Vellore, Tamil N\u0101du, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahaboobkhan","family":"Rasool","sequence":"additional","affiliation":[{"name":"Immunopathology Lab, School of Biosciences and Technology, Vellore Institute of Technology (VIT)","place":["Vellore, Tamil N\u0101du, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2025.115429","article-title":"Advancing insights into psoriasis: from pathogenesis to current and emerging therapies","volume":"165","author":"Gon\u00e7alves","year":"2025","journal-title":"Int Immunopharmacol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"164\u201391","DOI":"10.1007\/s12016-024-08991-7","article-title":"The Immunology of Psoriasis\u2014Current Concepts in Pathogenesis","volume":"66","author":"Sieminska","year":"2024","journal-title":"Clinical Reviews in Allergy & Immunology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1007\/s10555-006-7890-0","article-title":"Degradomics: systems biology of the protease web. 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