{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T21:23:56Z","timestamp":1793913836694,"version":"4.8.0"},"reference-count":70,"publisher":"American Society for Clinical Investigation","issue":"24","license":[{"start":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T00:00:00Z","timestamp":1671667200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CIHR-Genome Canada","award":["Canadian Rare Diseases: Models"],"award-info":[{"award-number":["Canadian Rare Diseases: Models"]}]},{"name":"CIHR-Genome Canada","award":["Mechanisms Network Catalyst Grant"],"award-info":[{"award-number":["Mechanisms Network Catalyst Grant"]}]},{"DOI":"10.13039\/501100002722","name":"AllerGen","doi-asserted-by":"crossref","award":["Emerging Clinician-Scientist Fellowship"],"award-info":[{"award-number":["Emerging Clinician-Scientist Fellowship"]}],"id":[{"id":"10.13039\/501100002722","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008154","name":"CAAIF","doi-asserted-by":"crossref","award":["Research Fellowship"],"award-info":[{"award-number":["Research Fellowship"]}],"id":[{"id":"10.13039\/100008154","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Primary Immune Deficiency Treatment Consortium","award":["Research Grant"],"award-info":[{"award-number":["Research Grant"]}]},{"DOI":"10.13039\/501100000245","name":"Michael Smith Foundation for Health Research","doi-asserted-by":"crossref","award":["Health Professional Investigator Award"],"award-info":[{"award-number":["Health Professional Investigator Award"]}],"id":[{"id":"10.13039\/501100000245","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,12,22]]},"abstract":"<jats:p>\n                    Primary atopic disorders are a group of inborn errors of immunity that skew the immune system toward severe allergic disease. Defining the biology underlying these extreme monogenic phenotypes reveals shared mechanisms underlying common polygenic allergic disease and identifies potential drug targets. Germline gain-of-function (GOF) variants in\n                    <jats:italic>JAK1<\/jats:italic>\n                    are a cause of severe atopy and eosinophilia. Modeling the\n                    <jats:italic>JAK1<\/jats:italic>\n                    <jats:sup>GOF<\/jats:sup>\n                    (p.A634D) variant in both zebrafish and human induced pluripotent stem cells (iPSCs) revealed enhanced myelopoiesis. RNA-Seq of\n                    <jats:italic>JAK1<\/jats:italic>\n                    <jats:sup>GOF<\/jats:sup>\n                    human whole blood, iPSCs, and transgenic zebrafish revealed a shared core set of dysregulated genes involved in IL-4, IL-13, and IFN signaling. Immunophenotypic and transcriptomic analysis of patients carrying a\n                    <jats:italic>JAK1<\/jats:italic>\n                    <jats:sup>GOF<\/jats:sup>\n                    variant revealed marked Th cell skewing. Moreover, long-term ruxolitinib treatment of 2 children carrying the\n                    <jats:italic>JAK1<\/jats:italic>\n                    <jats:sup>GOF<\/jats:sup>\n                    (p.A634D) variant remarkably improved their growth, eosinophilia, and clinical features of allergic inflammation. This work highlights the role of JAK1 signaling in atopic immune dysregulation and the clinical impact of JAK1\/2 inhibition in treating eosinophilic and allergic disease.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.150849","type":"journal-article","created":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T14:00:42Z","timestamp":1671631242000},"source":"Crossref","is-referenced-by-count":35,"title":["Human JAK1 gain of function causes dysregulated myelopoeisis and severe allergic inflammation"],"prefix":"10.1172","volume":"7","author":[{"given":"Catherine M.","family":"Biggs","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada."},{"name":"BC Children\u2019s Hospital, Vancouver, British Columbia, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Cordeiro-Santanach","sequence":"additional","affiliation":[{"name":"AGADA Biosciences Inc., Halifax, 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