{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T04:27:59Z","timestamp":1775017679002,"version":"3.50.1"},"reference-count":45,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T00:00:00Z","timestamp":1705622400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Endothelial protein C receptor (EPCR) is a receptor for the natural anti-coagulant activated protein C (aPC). It mediates the anti-inflammatory and barrier-protective functions of aPC through the cleavage of protease-activated receptor (PAR)1\/2. Allergic contact dermatitis is a common skin disease characterized by inflammation and defective skin barrier. This study investigated the effect of EPCR and 3K3A-aPC on allergic contact dermatitis using a contact hypersensitivity (CHS) model. CHS was induced using 1-Fluoro-2,4-dinitrobenzene in EPCR-deficient (KO) and matched wild-type mice and mice treated with 3K3A-aPC, a mutant form of aPC with diminished anti-coagulant activity. Changes in clinical and histological features, cytokines, and immune cells were examined. EPCRKO mice displayed more severe CHS, with increased immune cell infiltration in the skin and higher levels of inflammatory cytokines and IgE than wild-type mice. EPCR, aPC, and PAR1\/2 were expressed by the skin epidermis, with EPCR presenting almost exclusively in the basal layer. EPCRKO increased the epidermal expression of aPC and PAR1, whereas in CHS, their expression was reduced compared to wild-type mice. 3K3A-aPC reduced CHS severity in wild-type and EPCRKO mice by suppressing immune cell infiltration\/activation and inflammatory cytokines. In summary, EPCRKO exacerbated CHS, whereas 3K3A-aPC could reduce the severity of CHS in both EPCRKO and wild-type mice.<\/jats:p>","DOI":"10.3390\/ijms25021255","type":"journal-article","created":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T09:46:39Z","timestamp":1705657599000},"page":"1255","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Endothelial Protein C Receptor and 3K3A-Activated Protein C Protect Mice from Allergic Contact Dermatitis in a Contact Hypersensitivity Model"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8563-7216","authenticated-orcid":false,"given":"Meilang","family":"Xue","sequence":"first","affiliation":[{"name":"Sutton Arthritis Research Laboratory, Kolling Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2065, Australia"},{"name":"The Australian Arthritis and Autoimmune Biobank Collaborative (A3BC), Kolling Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2065, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher J.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Sutton Arthritis Research Laboratory, Kolling Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2065, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiyan","family":"Lin","sequence":"additional","affiliation":[{"name":"Sutton Arthritis Research Laboratory, Kolling Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2065, Australia"},{"name":"The Australian Arthritis and Autoimmune Biobank Collaborative (A3BC), Kolling Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2065, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4610-4898","authenticated-orcid":false,"given":"Ruilong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Sutton Arthritis Research Laboratory, Kolling Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2065, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hai Po H.","family":"Liang","sequence":"additional","affiliation":[{"name":"Sutton Arthritis Research Laboratory, Kolling Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2065, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hartmut","family":"Weiler","sequence":"additional","affiliation":[{"name":"Versiti Blood Research Institute, Milwaukee, WI 53226, USA"},{"name":"Department of Physiology, The Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John H.","family":"Griffin","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lyn","family":"March","sequence":"additional","affiliation":[{"name":"The Australian Arthritis and Autoimmune Biobank Collaborative (A3BC), Kolling Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2065, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"26486","DOI":"10.1016\/S0021-9258(18)47220-1","article-title":"Identification, cloning, and regulation of a novel endothelial cell protein c activated protein c receptor","volume":"269","author":"Fukudome","year":"1994","journal-title":"J. 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