Therapeutic Effects of Aβ-Specific Regulatory T Cells in Alzheimer’s Disease: A Study in 5xFAD Mice
The aging global population is placing an increasing burden on healthcare systems, and the social impact of Alzheimer’s disease (AD) is on the rise. However, the availability of safe and effective treatments for AD remains limited. Adoptive Treg therapy has been explored for treating neurodegenerati...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/2/783 |
| _version_ | 1797339871719718912 |
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| author | Seon-Young Park Juwon Yang Hyejin Yang Inhee Cho Jae Yoon Kim Hyunsu Bae |
| author_facet | Seon-Young Park Juwon Yang Hyejin Yang Inhee Cho Jae Yoon Kim Hyunsu Bae |
| author_sort | Seon-Young Park |
| collection | DOAJ |
| description | The aging global population is placing an increasing burden on healthcare systems, and the social impact of Alzheimer’s disease (AD) is on the rise. However, the availability of safe and effective treatments for AD remains limited. Adoptive Treg therapy has been explored for treating neurodegenerative diseases, including AD. To facilitate the clinical application of Treg therapy, we developed a Treg preparation protocol and highlighted the therapeutic effects of Tregs in 5xFAD mice. CD4<sup>+</sup>CD25<sup>+</sup> Tregs, isolated after Aβ stimulation and expanded using a G-rex plate with a gas-permeable membrane, were adoptively transferred into 5xFAD mice. Behavioral analysis was conducted using Y-maze and passive avoidance tests. Additionally, we measured levels of Aβ, phosphorylated tau (pTAU), and nitric oxide synthase 2 (NOS2) in the hippocampus. Real-time RT-PCR was employed to assess the mRNA levels of pro- and anti-inflammatory markers. Our findings indicate that Aβ-specific Tregs not only improved cognitive function but also reduced Aβ and pTAU accumulation in the hippocampus of 5xFAD mice. They also inhibited microglial neuroinflammation. These effects were observed at doses as low as 1.5 × 10<sup>3</sup> cells/head. Collectively, our results demonstrate that Aβ-specific Tregs can mitigate AD pathology in 5xFAD mice. |
| first_indexed | 2024-03-08T09:53:45Z |
| format | Article |
| id | doaj.art-5330ade391c94997b35d040fe9d5f36d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T09:53:45Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5330ade391c94997b35d040fe9d5f36d2024-01-29T13:54:14ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-01-0125278310.3390/ijms25020783Therapeutic Effects of Aβ-Specific Regulatory T Cells in Alzheimer’s Disease: A Study in 5xFAD MiceSeon-Young Park0Juwon Yang1Hyejin Yang2Inhee Cho3Jae Yoon Kim4Hyunsu Bae5Department of Science in Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of KoreaDepartment of Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of KoreaDepartment of Science in Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of KoreaDepartment of Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of KoreaInstitute of Life Science & Biotechnology, VT Bio. Co., Ltd., 16 Samseong-ro 76-gil, Gangnam-gu, Seoul 06185, Republic of KoreaDepartment of Science in Korean Medicine, College of Korean Medicine, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of KoreaThe aging global population is placing an increasing burden on healthcare systems, and the social impact of Alzheimer’s disease (AD) is on the rise. However, the availability of safe and effective treatments for AD remains limited. Adoptive Treg therapy has been explored for treating neurodegenerative diseases, including AD. To facilitate the clinical application of Treg therapy, we developed a Treg preparation protocol and highlighted the therapeutic effects of Tregs in 5xFAD mice. CD4<sup>+</sup>CD25<sup>+</sup> Tregs, isolated after Aβ stimulation and expanded using a G-rex plate with a gas-permeable membrane, were adoptively transferred into 5xFAD mice. Behavioral analysis was conducted using Y-maze and passive avoidance tests. Additionally, we measured levels of Aβ, phosphorylated tau (pTAU), and nitric oxide synthase 2 (NOS2) in the hippocampus. Real-time RT-PCR was employed to assess the mRNA levels of pro- and anti-inflammatory markers. Our findings indicate that Aβ-specific Tregs not only improved cognitive function but also reduced Aβ and pTAU accumulation in the hippocampus of 5xFAD mice. They also inhibited microglial neuroinflammation. These effects were observed at doses as low as 1.5 × 10<sup>3</sup> cells/head. Collectively, our results demonstrate that Aβ-specific Tregs can mitigate AD pathology in 5xFAD mice.https://www.mdpi.com/1422-0067/25/2/783Alzheimer’s diseaseregulatory T cellsAmyloid-β |
| spellingShingle | Seon-Young Park Juwon Yang Hyejin Yang Inhee Cho Jae Yoon Kim Hyunsu Bae Therapeutic Effects of Aβ-Specific Regulatory T Cells in Alzheimer’s Disease: A Study in 5xFAD Mice International Journal of Molecular Sciences Alzheimer’s disease regulatory T cells Amyloid-β |
| title | Therapeutic Effects of Aβ-Specific Regulatory T Cells in Alzheimer’s Disease: A Study in 5xFAD Mice |
| title_full | Therapeutic Effects of Aβ-Specific Regulatory T Cells in Alzheimer’s Disease: A Study in 5xFAD Mice |
| title_fullStr | Therapeutic Effects of Aβ-Specific Regulatory T Cells in Alzheimer’s Disease: A Study in 5xFAD Mice |
| title_full_unstemmed | Therapeutic Effects of Aβ-Specific Regulatory T Cells in Alzheimer’s Disease: A Study in 5xFAD Mice |
| title_short | Therapeutic Effects of Aβ-Specific Regulatory T Cells in Alzheimer’s Disease: A Study in 5xFAD Mice |
| title_sort | therapeutic effects of aβ specific regulatory t cells in alzheimer s disease a study in 5xfad mice |
| topic | Alzheimer’s disease regulatory T cells Amyloid-β |
| url | https://www.mdpi.com/1422-0067/25/2/783 |
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