{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:57:55Z","timestamp":1787237875395,"version":"build-2736575974"},"reference-count":63,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"108","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2025,6,6]]},"abstract":"<jats:p>Despite substantial advancements in psoriatic arthritis (PsA) treatment modalities, a considerable proportion of patients continue to experience persistent joint inflammation, unresponsive to the armamentarium of disease-modifying antirheumatic drugs. Identifying previously unknown biomarkers and targets for refractory disease is urgently needed. Here, using single-cell RNA sequencing of synovial fluid from 41 patients with PsA and 9 osteoarthritis (OA) controls, we mapped the immune landscape of the pathogenic synovial fluid in patients with PsA. Our analysis revealed profound alterations in the myeloid compartment, primarily in type 2 conventional dendritic cells and monocytes. A comparison of these myeloid programs in PsA patient groups identified elevated expression of genes associated with the immunoproteasome and major histocompatibility complex class I as a major perturbation in refractory patients. Functional in vivo and in vitro experiments using a selective immunoproteasome inhibitor attenuated the activated myeloid compartment and disease manifestations. Our research imparts critical insights into PsA pathogenesis, potentially paving a way for targeted therapeutic interventions in treatment-resistant patients.<\/jats:p>","DOI":"10.1126\/sciimmunol.adu0284","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T13:58:28Z","timestamp":1749218308000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":6,"title":["Dissection of the immune landscape in psoriatic arthritis defines immunoproteasome up-regulation in treatment resistance"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2848-7243","authenticated-orcid":true,"given":"Reut","family":"Tzemach","sequence":"first","affiliation":[{"name":"Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel."},{"name":"Department of Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv, 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