{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T06:42:05Z","timestamp":1793256125389,"version":"4.5.0"},"reference-count":47,"publisher":"American Society for Clinical Investigation","issue":"16","license":[{"start":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T00:00:00Z","timestamp":1661126400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P30AR075043,1K24AR077313"],"award-info":[{"award-number":["P30AR075043,1K24AR077313"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,22]]},"abstract":"<jats:p>\n                    Proprotein convertase subtilisin\/kexin type-9 (PCSK9) is a posttranslational regulator of the LDL receptor (LDLR). Recent studies have proposed a role for PCSK9 in regulating immune responses. Using RNA-Seq\u2013based variant discovery, we identified a possible psoriasis-susceptibility locus at 1p32.3, located within\n                    <jats:italic>PCSK9<\/jats:italic>\n                    (rs662145 C &gt; T). This finding was verified in independently acquired genomic and RNA-Seq data sets. Single-cell RNA-Seq (scRNA-Seq) identified keratinocytes as the primary source of\n                    <jats:italic>PCSK9<\/jats:italic>\n                    in human skin.\n                    <jats:italic>PCSK9<\/jats:italic>\n                    expression, however, was not uniform across keratinocyte subpopulations. scRNA-Seq and IHC demonstrated an epidermal gradient of PCSK9, with expression being highest in basal and early spinous layer keratinocytes and lowest in granular layer keratinocytes.\n                    <jats:italic>IL36G<\/jats:italic>\n                    expression followed the opposite pattern, with expression highest in granular layer keratinocytes.\n                    <jats:italic>PCSK9<\/jats:italic>\n                    siRNA knockdown experiments confirmed this inverse relationship between\n                    <jats:italic>PCSK9<\/jats:italic>\n                    and\n                    <jats:italic>IL36G<\/jats:italic>\n                    expression. Other immune genes were also linked to\n                    <jats:italic>PCSK9<\/jats:italic>\n                    expression, including\n                    <jats:italic>IL27RA<\/jats:italic>\n                    ,\n                    <jats:italic>IL1RL1<\/jats:italic>\n                    ,\n                    <jats:italic>ISG20<\/jats:italic>\n                    , and\n                    <jats:italic>STX3<\/jats:italic>\n                    . In both cultured keratinocytes and nonlesional human skin, homozygosity for\n                    <jats:italic>PCSK9<\/jats:italic>\n                    SNP rs662145 C &gt; T was associated with lower\n                    <jats:italic>PCSK9<\/jats:italic>\n                    expression and higher\n                    <jats:italic>IL36G<\/jats:italic>\n                    expression, when compared with heterozygous skin or cell lines. Together, these results support\n                    <jats:italic>PCSK9<\/jats:italic>\n                    as a psoriasis-susceptibility locus and establish a putative link between PCSK9 and inflammatory cytokine expression.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.141193","type":"journal-article","created":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T12:00:56Z","timestamp":1658404856000},"source":"Crossref","is-referenced-by-count":45,"title":["Proprotein convertase subtilisin\/kexin type 9 is a psoriasis-susceptibility locus that is negatively related to IL36G"],"prefix":"10.1172","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5735-7233","authenticated-orcid":true,"given":"Alexander","family":"Merleev","sequence":"first","affiliation":[{"name":"Department of Dermatology, University of California, Davis (UCD), Sacramento, California, 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