{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T19:55:56Z","timestamp":1793476556627,"version":"4.5.0"},"reference-count":68,"publisher":"American Society of Hematology","issue":"5","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,7,31]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Macrophage activation syndrome (MAS) is believed to be caused by inappropriate proliferation and activation of the mononuclear phagocytic system. Adult-onset Still disease (AOSD) is characterized by neutrophil activation and a cytokine storm, which can lead to the severe and potentially life-threatening complication of MAS. RNA sequencing revealed that neutrophils may play a distinct role and enhance the innate immunity of patients with AOSD with MAS (AOSD-MAS). In the CpG-induced secondary hemophagocytic lymphohistiocytosis (HLH) model, the depletion of neutrophils significantly reduced cytokine levels with effects comparable with monocyte depletion. Significant enrichment was observed in the type I\/II interferon and JAK-STAT pathways in neutrophils from patients with AOSD-MAS. Treatment of 10 patients with refractory AOSD-MAS with ruxolitinib led to the resolution of inflammatory parameters and clinical symptoms. RNA sequencing and ex vivo assays confirmed that ruxolitinib suppressed aberrant NETosis and STAT3\/STAT5 signaling. In vivo, PAD4 knockout further confirmed the pathogenic role of NETosis in a secondary HLH model. Moreover, the selective inhibition of STAT3 or STAT5 alleviated systemic inflammation. Ten functional variants were identified in genes related to the JAK-STAT pathway, however, their clinical relevance requires further validation. These findings suggest that ruxolitinib has the potential to facilitate disease remission in patients with refractory AOSD-MAS by broadly inhibiting JAK-STAT signaling and modulating neutrophil activation and NETosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2024024362","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T15:11:57Z","timestamp":1747667517000},"page":"612-627","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":28,"title":["Ruxolitinib targets JAK-STAT signaling to modulate neutrophil activation in refractory macrophage activation syndrome"],"prefix":"10.1182","volume":"146","author":[{"given":"Yuning","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 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