{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:31:11Z","timestamp":1790656271430,"version":"4.1.0"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Interstitial cystitis\/bladder pain syndrome (IC\/BPS), particularly the Hunner-type subtype (HIC), is a chronic inflammatory bladder disorder characterized by persistent inflammation and macrophage-driven immunometabolic dysregulation. CHI3L1, a secreted glycoprotein implicated in inflammation and tissue remodeling, is significantly upregulated in HIC and correlates with disease severity, but its mechanistic role in macrophage-mediated persistent inflammatory events (PIEs) remains poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study integrated multi-omics analyses, including bioinformatics of IC\/BPS transcriptomic datasets, a cyclophosphamide-induced IC\/BPS mouse model for\n                      <jats:italic>in vivo<\/jats:italic>\n                      validation, and\n                      <jats:italic>in vitro<\/jats:italic>\n                      functional assays involving CHI3L1 overexpression in macrophages. Transcriptomic, metabolomic, and molecular biology techniques were employed to evaluate metabolic shifts, inflammatory pathways, and transcription factor correlations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CHI3L1 expression was significantly upregulated in HIC patients, especially those with reduced bladder capacity, and correlated with inflammatory markers (IL-6, TNF\u03b1). In macrophages, CHI3L1 overexpression drove pro-inflammatory activation via NF-\u03baB and TNF pathways, promoted glycolysis, and suppressed mitochondrial oxidative phosphorylation (OXPHOS) and aspartate metabolism. Critically, CHI3L1 expression strongly correlated with the transcription factor MYC rather than STAT3 under inflammatory conditions, reinforcing M1 polarization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CHI3L1 exacerbates PIEs in HIC by reprogramming macrophage metabolism toward glycolysis and sustaining inflammation via MYC signaling. These findings establish CHI3L1 as a central regulator of chronic inflammation in HIC and highlight its potential as a therapeutic target for disrupting pathological immune-metabolic cycles.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1716297","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T05:22:25Z","timestamp":1769664145000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Enhanced CHI3L1 promotes macrophage activation in persistent inflammatory events of ulcerative interstitial cystitis"],"prefix":"10.3389","volume":"17","author":[{"given":"Wei","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Urology, The Affiliated Hospital of Qingdao University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yize","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of 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