{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T20:15:40Z","timestamp":1781554540908,"version":"3.54.5"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100020480","name":"CSL Limited","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020480","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Sarcoidosis is a multisystem chronic inflammatory disorder of unknown etiology that primarily affects the lungs and currently has no cure. Macrophages are central to granuloma formation, and \u03b2c cytokines tightly regulate their activation and function. This study investigates the role of the \u03b2c receptor in granuloma development and evaluates \u03b2c antagonism as a potential therapeutic strategy for sarcoidosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We utilized an\n                      <jats:italic>in vitro<\/jats:italic>\n                      model of human granuloma formation using sarcoidosis patient human peripheral blood mononuclear cells (PBMCs) and an\n                      <jats:italic>in vivo<\/jats:italic>\n                      vimentin-induced pulmonary sarcoidosis model in unique humanized \u03b2c transgenic (h\u03b2cTg) mice to assess the efficacy of \u03b2c antagonism in reducing granuloma formation and evaluate the underlying mechanism of action.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Anti-\u03b2c receptor antibody, CSL311, significantly reduced the formation of human granulomas from PBMCs exposed to purified protein derivative and decreased the pro-inflammatory cytokine production by the granulomas. Mechanistically, CSL311 inhibited hyperactivation of mTOR signaling and reduced lipid droplet formation in granuloma macrophages. In h\u03b2cTg mice challenged with vimentin, CSL311 effectively reduced both granuloma size and immune cell infiltration in the lung. RNA sequencing analysis of lung tissue further showed that CSL311 treatment suppressed the activation of vimentin-induced inflammatory, fibrotic, and lipid metabolic pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We identified that \u03b2c cytokines are critical regulators in driving inflammatory and metabolic processes that lead to granuloma formation in sarcoidosis. Precisely targeting the \u03b2c receptor effectively disrupts these pathogenic networks and offers a promising new strategy for mitigating sarcoidosis immunopathology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1733060","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T05:17:31Z","timestamp":1765862251000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["\u03b2c receptor antagonism mitigates sarcoidosis granuloma formation by targeting inflammatory signals and aberrant lipid metabolism"],"prefix":"10.3389","volume":"16","author":[{"given":"Hao","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damon 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