{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T19:56:05Z","timestamp":1793476565110,"version":"4.5.0"},"reference-count":26,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guangdong Basic and Applied Basic Research Fund","award":["2023A1515140033"],"award-info":[{"award-number":["2023A1515140033"]}]},{"name":"Guangdong Basic and Applied Basic Research Fund","award":["2024A1515140175"],"award-info":[{"award-number":["2024A1515140175"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81872144"],"award-info":[{"award-number":["81872144"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Dongguan Eighth People\u2019s Hospital doctoral research start-up fund project","award":["DBBS2023001"],"award-info":[{"award-number":["DBBS2023001"]}]},{"name":"Dongguan Eighth People\u2019s Hospital doctoral research start-up fund project","award":["DBBS2023003"],"award-info":[{"award-number":["DBBS2023003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>NLRP3-associated autoinflammatory diseases (NLRP3-AIDs) are rare autoinflammatory disorders caused by uncontrolled inflammasome activation. While IL-1\u03b2 blockade is first-line therapy, many patients respond inadequately, highlighting a need for alternative strategies. Transcriptomic analysis was performed on immune cells from a patient with an NLRP3 L573W mutation. Functional validation of CD177 as a downstream effector of NLRP3 activation was conducted. A novel NLRP3 L573W knock-in mouse model was established. Correlation between CD177 expression, disease severity, neutrophilia, and tissue damage was assessed. Therapeutic efficacy of siRNA-mediated CD177 silencing was evaluated and compared with IL-1\u03b2 blockade. CD177, a neutrophil-specific protein, was significantly upregulated in NLRP3-mutant cells and confirmed as a direct downstream effector of NLRP3 activation. The NLRP3 L573W knock-in mouse recapitulated human disease heterogeneity, from mild self-limited inflammation to severe multi-organ pathology. CD177 expression correlated with disease severity, neutrophilia, and tissue damage. siRNA-mediated CD177 silencing attenuated systemic inflammation, reduced neutrophil infiltration and cytokine levels (IL-1\u03b2, IL-6, TNF\u03b1), and ameliorated multi-organ damage, with effects comparable to or exceeding those of IL-1\u03b2 blockade. CD177 is a non-canonical amplifier of NLRP3-driven inflammation. Targeting CD177 represents a superior therapeutic strategy for NLRP3-AIDs, including IL-1\u03b2-refractory cases.<\/jats:p>","DOI":"10.3390\/ijms27062841","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T17:02:43Z","timestamp":1774026163000},"page":"2841","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting CD177: A Novel Therapeutic Strategy for NLRP3-Associated Autoinflammatory Diseases"],"prefix":"10.3390","volume":"27","author":[{"given":"Yinghua","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Genetic Medicine, Dongguan Children\u2019s Hospital Affiliated to Guangdong Medical University, Dongguan 523325, China"},{"name":"Key Laboratory for Children\u2019s Genetics and Infectious Diseases of Dongguan, Dongguan 523323, China"},{"name":"Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan 523325, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Dongguan Children\u2019s Hospital Affiliated to Guangdong Medical University, Dongguan 523325, China"},{"name":"Key Laboratory for Children\u2019s Genetics and Infectious Diseases of Dongguan, Dongguan 523323, China"},{"name":"Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan 523325, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siping","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Dongguan Children\u2019s Hospital Affiliated to Guangdong Medical University, Dongguan 523325, China"},{"name":"Key Laboratory for Children\u2019s Genetics and Infectious Diseases of Dongguan, Dongguan 523323, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihua","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Dongguan Children\u2019s Hospital Affiliated to Guangdong Medical University, Dongguan 523325, China"},{"name":"Key Laboratory for Children\u2019s Genetics and Infectious Diseases of Dongguan, Dongguan 523323, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaixue","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Dongguan Children\u2019s Hospital Affiliated to Guangdong Medical University, Dongguan 523325, China"},{"name":"Key Laboratory for Children\u2019s Genetics and Infectious Diseases of Dongguan, Dongguan 523323, China"},{"name":"Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan 523325, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fen","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Dongguan Children\u2019s Hospital Affiliated to Guangdong Medical University, Dongguan 523325, China"},{"name":"Key Laboratory for Children\u2019s Genetics and Infectious Diseases of Dongguan, Dongguan 523323, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Dongguan Children\u2019s Hospital Affiliated to Guangdong Medical University, Dongguan 523325, China"},{"name":"Key Laboratory for Children\u2019s Genetics and Infectious Diseases of Dongguan, Dongguan 523323, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongjun","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baimao","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Dongguan Children\u2019s Hospital Affiliated to Guangdong Medical University, Dongguan 523325, China"},{"name":"Key Laboratory for Children\u2019s Genetics and Infectious Diseases of Dongguan, Dongguan 523323, China"},{"name":"Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan 523325, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Dongguan Children\u2019s Hospital Affiliated to Guangdong Medical University, Dongguan 523325, China"},{"name":"Key Laboratory for Children\u2019s Genetics and Infectious Diseases of Dongguan, Dongguan 523323, China"},{"name":"Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan 523325, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Dongguan Children\u2019s Hospital Affiliated to Guangdong Medical University, Dongguan 523325, China"},{"name":"Key Laboratory for Children\u2019s Genetics and Infectious Diseases of Dongguan, Dongguan 523323, China"},{"name":"Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan 523325, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1093\/intimm\/dxz047","article-title":"Low-frequency mosaicism in cryopyrin-associated periodic fever syndrome: Mosaicism in systemic autoinflammatory diseases","volume":"31","author":"Nishikomori","year":"2019","journal-title":"Int. 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