Adoptive therapy with amyloid-P specific regulatory T cells alleviates Alzheimer's disease
DC Field | Value | Language |
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dc.contributor.author | Yang, HyeJin | - |
dc.contributor.author | Park, Seon-Young | - |
dc.contributor.author | Baek, Hyunjung | - |
dc.contributor.author | Lee, Chanju | - |
dc.contributor.author | Chung, Geehoon | - |
dc.contributor.author | Liu, Xiao | - |
dc.contributor.author | Lee, Ji Hwan | - |
dc.contributor.author | Kim, Byungkyu | - |
dc.contributor.author | Kwon, Minjin | - |
dc.contributor.author | Choi, Hyojung | - |
dc.contributor.author | Kim, Hyung Joon | - |
dc.contributor.author | Kim, Jae Yoon | - |
dc.contributor.author | Kim, Younsub | - |
dc.contributor.author | Lee, Ye-Seul | - |
dc.contributor.author | Lee, Gaheon | - |
dc.contributor.author | Kim, Sun Kwang | - |
dc.contributor.author | Kim, Jin Su | - |
dc.contributor.author | Chang, Young -Tae | - |
dc.contributor.author | Jung, Woo Sang | - |
dc.contributor.author | Kim, Kyung Hwa | - |
dc.contributor.author | Bae, Hyunsu | - |
dc.date.accessioned | 2023-01-19T00:40:34Z | - |
dc.date.available | 2023-01-19T00:40:34Z | - |
dc.date.created | 2023-01-18 | - |
dc.date.issued | 2022-11 | - |
dc.identifier.issn | 1838-7640 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/86659 | - |
dc.description.abstract | Rationale: Neuroinflammation is a primary feature of Alzheimer's disease (AD), for which an increasing number of drugs have been specifically developed. The present study aimed to define the therapeutic impact of a specific subpopulation of T cells that can suppress excessive inflammation in various immune and inflammatory disorders, namely, CD4+CD25+Foxp3+ regulatory T cells (Tregs).Methods: To generate AP antigen-specific Tregs (AP+ Tregs), AP 1-42 peptide was applied in vivo and subsequent in vitro splenocyte culture. After isolating Tregs by magnetic bead based purification method, AP+ Tregs were adoptively transferred into 3xTg-AD mice via tail vein injection. Therapeutic efficacy was confirmed with behavior test, Western blot, quantitative real-time PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry staining (IHC). In vitro suppression assay was performed to evaluate the suppressive activity of AP+ Tregs using flow cytometry. Thy1.1+ Treg trafficking and distribution was analyzed to explore the infused Tregs migration into specific organs in an antigen-driven manner in AD mice. We further assessed cerebral glucose metabolism using 18F-FDG-PET, an imaging approach for AD biological definition. Subsequently, we evaluated the migration of AP+ Tregs toward AP activated microglia using live cell imaging, chemotaxis, antibody blocking and migration assay.Results: We showed that AP-stimulated Tregs inhibited microglial proinflammatory activity and modulated the microglial phenotype via bystander suppression. Single adoptive transfer of AP+ Tregs was enough to induce amelioration of cognitive impairments, AP accumulation, hyper-phosphorylation of tau, and neuroinflammation during AD pathology. Moreover, AP-specific Tregs effectively inhibited inflammation in primary microglia induced by AP exposure. It may indicate bystander suppression in which AP-specific Tregs promote immune tolerance by secreting cytokines to modulate immune responses during neurodegeneration.Conclusions: The administration of AP antigen-specific regulatory T cells may represent a new cellular therapeutic strategy for AD that acts by modulating the inflammatory status in AD. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | IVYSPRING INT PUBL | - |
dc.relation.isPartOf | THERANOSTICS | - |
dc.title | Adoptive therapy with amyloid-P specific regulatory T cells alleviates Alzheimer's disease | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000891576100002 | - |
dc.identifier.doi | 10.7150/thno.75965 | - |
dc.identifier.bibliographicCitation | THERANOSTICS, v.12, no.18, pp.7668 - 7680 | - |
dc.description.isOpenAccess | Y | - |
dc.identifier.scopusid | 2-s2.0-85141963769 | - |
dc.citation.endPage | 7680 | - |
dc.citation.startPage | 7668 | - |
dc.citation.title | THERANOSTICS | - |
dc.citation.volume | 12 | - |
dc.citation.number | 18 | - |
dc.contributor.affiliatedAuthor | Kim, Younsub | - |
dc.contributor.affiliatedAuthor | Lee, Ye-Seul | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | Neuroinflammation | - |
dc.subject.keywordAuthor | antigen-specific Tregs | - |
dc.subject.keywordAuthor | adoptive transfer | - |
dc.subject.keywordAuthor | microglia | - |
dc.subject.keywordAuthor | bystander suppression | - |
dc.subject.keywordPlus | MOUSE MODEL | - |
dc.subject.keywordPlus | PROGRESSION | - |
dc.subject.keywordPlus | MICROGLIA | - |
dc.subject.keywordPlus | DEPLETION | - |
dc.subject.keywordPlus | RESPONSES | - |
dc.subject.keywordPlus | BRAIN | - |
dc.relation.journalResearchArea | Research & Experimental Medicine | - |
dc.relation.journalWebOfScienceCategory | Medicine, Research & Experimental | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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