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Most NMOSD patients present with anti-aquaporin-4 autoantibodies (AQP4-IgG), which trigger acute neuroinflammation and astrocyte damage through classical complement pathway activation and immune cell recruitment, yet AQP4-IgG alone does not fully account for NMOSD pathogenesis, suggesting additional contributing mechanisms. Emerging evidence highlights the critical role of innate immune cells\u2014macrophages, neutrophils, eosinophils, and natural killer cells\u2014in NMOSD lesion development, in which they amplify inflammation through cytokine release, antibody-dependent cellular cytotoxicity, and immune cell recruitment, ultimately exacerbating CNS damage. Importantly, recent advancements in NMOSD therapies have incorporated targeting innate immune responses, including interleukin-6 and complement inhibitors, and neutrophil and eosinophil modulators, enhancing treatment efficacy. This review explores the multifaceted roles of innate immune cells, their interactions with AQP4-IgG, and their contribution to disease progression. In summary, targeting innate immune pathways offers an alternative strategy to mitigate inflammation and damage in CNS.<\/jats:p>","DOI":"10.1093\/jleuko\/qiaf068","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T07:57:46Z","timestamp":1747295866000},"source":"Crossref","is-referenced-by-count":2,"title":["Detrimental roles of innate immune cells in neuromyelitis optica spectrum disorder: Pathogenesis and therapeutic targeting"],"prefix":"10.1093","volume":"117","author":[{"given":"Kar Min","family":"Loh","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya , Lembah Pantai, Kuala Lumpur 50603 ,","place":["Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi Ying","family":"Cheok","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya , Lembah Pantai, Kuala Lumpur 50603 ,","place":["Malaysia"]},{"name":"Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore , Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting Fang","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya , Lembah Pantai, Kuala Lumpur 50603 ,","place":["Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung Yeng","family":"Looi","sequence":"additional","affiliation":[{"name":"School of Biosciences, Faculty of Health & Medical Sciences, Taylor's University , Subang Jaya, Selangor 47500 ,","place":["Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1082-1956","authenticated-orcid":false,"given":"Won Fen","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya , 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