{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T05:13:57Z","timestamp":1765084437311,"version":"3.46.0"},"reference-count":55,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science and Technology Development Fund, Macao S.A.R.","award":["0089\/2022\/AFJ"],"award-info":[{"award-number":["0089\/2022\/AFJ"]}]},{"name":"Multi-Year Research Grant from University of Macau","award":["MYRG2018-00093-FHS"],"award-info":[{"award-number":["MYRG2018-00093-FHS"]}]},{"DOI":"10.13039\/501100006469","name":"FDCT","doi-asserted-by":"crossref","award":["0086\/2022\/AFJ"],"award-info":[{"award-number":["0086\/2022\/AFJ"]}],"id":[{"id":"10.13039\/501100006469","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Multi-Year Research Grant from University of Macau","award":["MYRG-GRG2023-00144-FHS-UMDF"],"award-info":[{"award-number":["MYRG-GRG2023-00144-FHS-UMDF"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>B-cell leukemia\/lymphoma protein 3 (Bcl3), a member of the I\u03baB family proteins, regulates the transcriptional activities of the NF-\u03baB family of transcription factors. It is known that aberrant Bcl3 activities induce malignancies of both hematologic and non-hematologic origins. Overexpressed, mutated and\/or phosphorylated Bcl3 has been implicated in several cancers due to its altered transcriptional activities. However, the physiological function of Bcl3 in immune homeostasis remained elusive to date. In this study, Bcl3 knockout zebrafish were generated to investigate its role in immune regulation. Bcl3 deficient zebrafish exhibited growth retardation and significantly reduced survival. Histological analyses revealed the absence of Hassall bodies in the thymus and hepatocellular nuclear abnormalities, indicating compromised integrity of the immune organs. Zebrafish with Bcl3 deficiency further showed enhanced immune responses and increased susceptibility to both bacterial and viral infections, resulting in significantly elevated levels of pro-inflammatory cytokines il1b, il6, il8, and tnfa. Treatment with the anti-inflammatory drug dexamethasone (Dex) effectively alleviated inflammation, downregulated pro-inflammatory cytokine expressions and improved survival. Collectively, our findings demonstrate Bcl3 as a key regulator of immune activation in vivo, highlighting its role in maintaining immune homeostasis and promoting organismal survival.<\/jats:p>","DOI":"10.3390\/cells14241935","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T15:11:24Z","timestamp":1764947484000},"page":"1935","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bcl3 Deficiency Leads to Hyperinflammation in Zebrafish"],"prefix":"10.3390","volume":"14","author":[{"given":"Chengjian","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau SAR, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nana","family":"Ai","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau SAR, China"},{"name":"Centre of Reproduction, Development and Aging (CRDA), Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau SAR, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4296-1585","authenticated-orcid":false,"given":"Wei","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau SAR, China"},{"name":"Centre of Reproduction, Development and Aging (CRDA), Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau SAR, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1984-2713","authenticated-orcid":false,"given":"Vivien Ya-Fan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau SAR, China"},{"name":"Cancer Centre, Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau SAR, China"},{"name":"MoE Frontiers Science Center for Precision Oncology, University of Macau, Avenida da Universidade, Taipa, Macau SAR, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"ref_1","first-page":"2057","article-title":"Molecular characterization of the t(14;19)(q32;q13) translocation in chronic lymphocytic leukemia","volume":"7","author":"Ohno","year":"1993","journal-title":"Leukemia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5984","DOI":"10.4049\/jimmunol.1300611","article-title":"The tumor promoter and NF-kappaB modulator Bcl-3 regulates splenic B cell development","volume":"191","author":"Zhang","year":"2013","journal-title":"J. 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