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While conventional \u2018gold standard\u2019 animal models have been central to autoimmune drug discovery, there is increasing recognition that addressing unmet medical needs requires models capable of capturing patient pathophysiology beyond the scope of these classical systems. Accordingly, models that reflect human disease mechanisms not reproducible in conventional animals are becoming increasingly important. Humanized mice are immunodeficient mice transplanted with human immune cells, hepatocytes, thymic tissue, and other components to create a human-like biological environment that cannot be replicated in wild-type mice. Research on humanized mice has advanced through efforts to reconstitute a diverse human immune system in mice, together with accumulating knowledge of patient-specific factors such as autoantibodies and autoreactive T cells. Additionally, single-cell analyses and human tissue studies are underway to recreate the human-specific disease phenomena in humanized mice. In this review, immune-system-humanized mice are used to provide a comprehensive overview of recent advances in immune-system-humanized mouse technologies, their applications to immune-related disease models, and their current utilization in drug discovery research.<\/jats:p>","DOI":"10.1186\/s41232-026-00427-3","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T11:15:34Z","timestamp":1780658134000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Advancement of humanized mice and leading applications in immunological disease models"],"prefix":"10.1186","volume":"46","author":[{"given":"Satoru","family":"Munakata","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Imura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sota","family":"Fujimori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryota","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piruzyan","family":"Mariam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzo","family":"Koda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"427_CR1","doi-asserted-by":"crossref","unstructured":"Loewa A, Feng JJ, Hedtrich S. 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