{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T14:34:04Z","timestamp":1782398044998,"version":"3.54.5"},"reference-count":38,"publisher":"American Society for Clinical Investigation","issue":"22","funder":[{"name":"Strategic Pharma-Academic Research Consortium","award":["2986"],"award-info":[{"award-number":["2986"]}]},{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"crossref","award":["R01 AI078994"],"award-info":[{"award-number":["R01 AI078994"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,11,15]]},"abstract":"<jats:p>\n                    Juvenile dermatomyositis (JDM) is a debilitating pediatric autoimmune disease manifesting with characteristic rash and muscle weakness. To delineate signaling abnormalities in JDM, mass cytometry was performed with PBMCs from treatment-naive JDM patients and controls. NK cell percentages were lower while frequencies of naive B cells and naive CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells were higher in JDM patients than in controls. These cell frequency differences were attenuated with cessation of active disease. A large number of signaling differences were identified in treatment-naive JDM patients compared with controls. Classification models incorporating feature selection demonstrated that differences in phospholipase C\u03b32 (PLC\u03b32) phosphorylation comprised 10 of 12 features (i.e., phosphoprotein in a specific immune cell subset) distinguishing the 2 groups. Because NK cells represented 5 of these 12 features, further studies focused on the PLC\u03b32 pathway in NK cells, which is responsible for stimulating calcium flux and cytotoxic granule movement. No differences were detected in upstream signaling or total PLC\u03b32 protein levels. Hypophosphorylation of PLC\u03b32 and downstream mitogen-activated protein kinase-activated protein kinase 2 were partially attenuated with cessation of active disease. PLC\u03b32 hypophosphorylation in treatment-naive JDM patients resulted in decreased calcium flux. The identification of dysregulation of PLC\u03b32 phosphorylation and decreased calcium flux in NK cells provides potential mechanistic insight into JDM pathogenesis.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.123236","type":"journal-article","created":{"date-parts":[[2018,11,14]],"date-time":"2018-11-14T11:01:38Z","timestamp":1542193298000},"source":"Crossref","is-referenced-by-count":29,"title":["Dysregulated NK cell PLC\u03b32 signaling and activity in juvenile dermatomyositis"],"prefix":"10.1172","volume":"3","author":[{"given":"Allison A.","family":"Throm","sequence":"first","affiliation":[{"name":"Division of Pediatric Rheumatology, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA."},{"name":"Department of Biomedical Engineering, Washington University, St. Louis, Missouri, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua B.","family":"Alinger","sequence":"additional","affiliation":[{"name":"Division of Pediatric Rheumatology, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanette T.","family":"Pingel","sequence":"additional","affiliation":[{"name":"Division of Pediatric Rheumatology, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allyssa L.","family":"Daugherty","sequence":"additional","affiliation":[{"name":"Division of Pediatric Rheumatology, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren M.","family":"Pachman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA."},{"name":"Stanley Manne Children\u2019s Research Institute, Cure JM Center of Excellence in Juvenile Myositis Research, Department of Pediatrics, Ann & Robert H. 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