title: Neuroprotective effects of CD4+CD25+Foxp3+ regulatory T cells in a 3xTg-AD Alzheimer's disease model.
abstract: Alzheimer's disease patients display neuropathological lesions, including the accumulation of amyloid-beta (Aβ) peptide and neurofibrillary tangles. Although the mechanisms causing the neurodegenerative process are largely unknown, increasing evidence highlights a critical role of immunity in the pathogenesis of Alzheimer's disease. In the present study, we investigated the role of regulatory T cells (Tregs) on Alzheimer's disease progression. First, we explored the effect of Tregs (CD4+CD25+ T cells) and Teffs (CD4+CD25- T cells) in an adoptive transfer model. Systemic transplantation of purified Tregs into 3xTg-AD mice improved cognitive function and reduced deposition of Aβ plaques. In contrast, adoptive transfer of Teffs diminished behavioral function and cytokine production. Next, we transiently depleted Treg population using an anti-CD25 antibody (PC61). Depletion of Tregs for four months resulted in a marked aggravation of the spatial learning deficits of six-month-old 3xTg-AD mice. Additionally, it resulted in decreasing glucose metabolism, as assessed by positron emission tomography (PET) with 18F-2 fluoro-2-deoxy-D-glucose ([F-18] FDG) neuroimaging. Importantly, the deposition of Aβ plaques and microglia/macrophage was increased in the hippocampal CA1 and CA3 regions of the Treg depleted 3xTg-AD compared to the vehicle-treated 3xTg-AD group. Our finding suggested that systemic Treg administration ameliorates disease progression and could be an effective Alzheimer's disease treatment.
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Hyunjung
authors.initials: H
authors.lastname: Baek
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Minsook
authors.initials: M
authors.lastname: Ye
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Geun-Hyung
authors.initials: GH
authors.lastname: Kang
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Chanju
authors.initials: C
authors.lastname: Lee
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Gihyun
authors.initials: G
authors.lastname: Lee
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Da Bin
authors.initials: DB
authors.lastname: Choi
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Jung
authors.affiliation: K-herb Research Center, Korea Institute of Oriental Medicine, Yuseongdae-ro, Yuseong-gu, Daejeon, Republic of Korea.
authors.forename: Hyunseong
authors.initials: H
authors.lastname: Kim
authors.affiliation: Division of RI Research, Korea Institute of Radiological & Medical Sciences University of Science & Technology, Gongneug-dong, Nowon-ku, Seoul, Republic of Korea.
authors.forename: Seonhwa
authors.initials: S
authors.lastname: Lee
authors.affiliation: Division of RI Research, Korea Institute of Radiological & Medical Sciences University of Science & Technology, Gongneug-dong, Nowon-ku, Seoul, Republic of Korea.
authors.forename: Jin Su
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Acupuncture and Meridian Science Research Center, College of Korean Medical Science Graduate School, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Acupuncture and Meridian Science Research Center, College of Korean Medical Science Graduate School, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Insop
authors.initials: I
authors.lastname: Shim
authors.affiliation: Department of Biotechnology, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Hyunsu
authors.initials: H
authors.lastname: Bae
mesh_terms: D019264:Adoptive Transfer / Q000379:methods*; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D000818:Animals; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007859:Learning Disabilities / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D008297:Male; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D049268:Positron-Emission Tomography / Q000379:methods; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism / Q000637:transplantation*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D005947:Glucose
keywords: Alzheimer’s disease; Immune response; Immunity; Immunology and Microbiology Section; amyloid-beta (Aβ) pathology; regulatory T cells (Treg)