{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T18:09:18Z","timestamp":1788804558353,"version":"build-2803163510"},"reference-count":74,"publisher":"American Society for Clinical Investigation","issue":"17","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,8]]},"abstract":"<jats:p>\n                    Gain-of-function (GOF) variants in STAT3 cause a complex disorder characterized by early-onset autoimmunity, lymphoproliferation, recurrent infections, and immune dysregulation. In both primary human and mouse models of STAT3 GOF, CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells have been implicated as pathogenic drivers of autoimmunity, though the exact mechanisms remain poorly understood. Here, we found that in patients with STAT3 GOF, CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells exist in an activated state. Functional assessment revealed that naive CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells have an increased capacity for IFN-\u03b3 and TNF-\u03b1 production, with type I and type II IFN transcriptional signatures. Evaluation of immunoregulatory pathways revealed dysregulation of the purinergic signaling axis in CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells: CD39 was increased, whereas downstream purinergic family members, CD73 and the adenosine receptor A\n                    <jats:sub>2A<\/jats:sub>\n                    R, were downregulated, impairing the potential to produce or sense immunosuppressive adenosine. Evaluation of the impact of precision therapy, in the form of JAK inhibition, at a cellular and functional level revealed partial normalization of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell dysregulation in patients, including aberrant cytokine production. Our study suggests that a dysregulated purinergic signaling axis plays a key role in CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell dysregulation in STAT3 GOF and may have implications for other rare monogenic immune disorders and common inflammatory disorders.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.202959","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T18:01:06Z","timestamp":1788804066000},"source":"Crossref","is-referenced-by-count":0,"title":["Impaired regulation by purinergic signaling axis contributes to CD8+ T cell dysregulation in STAT3 gain of function"],"prefix":"10.1172","volume":"11","author":[{"given":"Jose S.","family":"Campos Duran","sequence":"first","affiliation":[{"name":"Division of Allergy and Immunology, Department of Pediatrics, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA."},{"name":"Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA."},{"name":"Institute for Immunology and Immune Health, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montana S.","family":"Knight","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Department of Pediatrics, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA."},{"name":"Department of Biomedical and Health Informatics, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4981-5721","authenticated-orcid":true,"given":"Samir U.","family":"Sayed","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Department of Pediatrics, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan C.","family":"Dalalo","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Department of Pediatrics, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea A.","family":"Mauracher","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Department of Pediatrics, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peyton","family":"Conrey","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Department of Pediatrics, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron B.","family":"Schultz","sequence":"additional","affiliation":[{"name":"Department of 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