{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:56:51Z","timestamp":1791197811645,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI185412"],"award-info":[{"award-number":["AI185412"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Integration of intracellular signalling and metabolic reprogramming is critical for macrophage polarisation and the induction of pro\u2010 or anti\u2010inflammatory responses. However, the molecular switches that govern these processes remain incompletely defined. While 4\u20101BB ligand (4\u20101BBL), a member of the TNF superfamily, is known to promote sustained pro\u2010inflammatory responses in macrophages, its role in anti\u2010inflammatory macrophage responses has not been fully elucidated. This study identifies that 4\u20101BBL serves as a negative regulator of anti\u2010inflammatory macrophage polarisation. Genetic deletion or pharmacological inhibition of 4\u20101BBL significantly enhanced the expression of anti\u2010inflammatory cytokines and markers in mouse macrophages. In IL\u20104R signalling, 4\u20101BBL restrained Janus kinase 1 (JAK1) and signal transducer and activator of transcription 6 (STAT6) phosphorylation, thereby modulating transcriptional programmes associated with anti\u2010inflammatory macrophage activation. Consistently, 4\u20101BBL deficiency elevated mitochondrial oxidative phosphorylation and fatty acid oxidation, accompanied by increased expression of metabolic genes in anti\u2010inflammatory macrophages. Transcriptomic analysis further revealed a shift towards anti\u2010inflammatory and oxidative metabolic gene signatures in IL\u20104\u2010treated 4\u20101BBL\u2010deficient macrophages. Importantly, the inhibition of 4\u20101BBL signalling also augmented anti\u2010inflammatory responses in human monocytes and facilitated the transition from pro\u2010inflammatory to anti\u2010inflammatory phenotypes. Collectively, these findings establish 4\u20101BBL as a crucial molecular switch that regulates macrophage polarisation by integrating inflammatory signalling with metabolic reprogramming, highlighting 4\u20101BBL as a potential therapeutic target for promoting inflammation resolution.<\/jats:p>","DOI":"10.1111\/imm.70173","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T08:01:05Z","timestamp":1785139265000},"page":"434-443","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>4\u20101BBL<\/scp>\n                    Suppresses Anti\u2010Inflammatory Responses by Regulating Metabolic Reprogramming of Macrophages"],"prefix":"10.1111","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9778-1963","authenticated-orcid":false,"given":"Young Jun","family":"Kang","sequence":"first","affiliation":[{"name":"Molecular Medicine Research Institute  Sunnyvale California 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