{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:03:19Z","timestamp":1790017399773,"version":"4.0.1"},"posted":{"date-parts":[[2026,2,13]]},"group-title":"Immunology","reference-count":83,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["236-12-25"],"award-info":[{"award-number":["236-12-25"]}],"id":[{"id":"https:\/\/ror.org\/01x5qb890","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Commonwealth of Virginia Center on Aging - Alzheimer's and Related Disease Research Award Fund","award":["21-1"],"award-info":[{"award-number":["21-1"]}]},{"award":["P30 CA016059"],"award-info":[{"award-number":["P30 CA016059"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["U01AG076481"],"award-info":[{"award-number":["U01AG076481"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Traumatic brain injury (TBI) is a significant risk factor for the development of Alzheimer\u2019s disease (AD) and related dementia. In both TBI and AD, inflammation plays a pivotal role. It is known that NLRP3 inflammasome plays an important role in pathogenesis of AD while TBI triggers activation of NLRP3 inflammasome in the brain. To evaluate the importance of NLRP3 inflammasome in mediating TBI-induced immune response in the context of predisposition of AD, we have examined the immune profiles in the brain using a novel transgenic AD mouse line with the NLRP3 gene deleted. Briefly, a group of 4 months old male and female 3xTg and 3xTg\/NLRP3\n                  <jats:sup>-\/-<\/jats:sup>\n                  mice received a moderate lateral fluid percussive injury or sham. Immune cell phenotypes and cytokine gene expression were assessed at 3- and 7-days post injury (dpi). We found that NLRP3 gene deletion counteracted injury-induced alteration of immune response in AD mice with a significant sex-related difference. Specifically, TBI induced a significant brain infiltration of neutrophils, macrophages and \u03b3\u03b4 T-cells in 3xTg mice in both sexes at 3dpi, and NLRP3 gene deletion blocked this injury effect only in males not in females. NLRP3 gene deletion also blocked injury-enhanced IL-1\u03b2, TNF-\u03b1 gene expression in male AD mice, but not in female mice. In conclusion, our study has confirmed that TBI significantly alters the immune response in 3xTg-AD mice and NLRP3 inflammasome is important in mediating these TBI-induced changes with significant sex-related differences.\n                <\/jats:p>","DOI":"10.64898\/2026.02.11.705384","type":"posted-content","created":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T07:05:16Z","timestamp":1771052716000},"source":"Crossref","is-referenced-by-count":1,"title":["Deletion of NLRP3 gene blocks traumatic brain injury induced abnormal immune response in 3xTg AD mice"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7059-9173","authenticated-orcid":false,"given":"Jakob","family":"Green","sequence":"first","affiliation":[{"name":"Department of Neuroscience and Anatomy, School of Pharmacy, Virginia Commonwealth University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of 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