1. B lymphocytes ameliorate Alzheimer's disease-like neuropathology via interleukin-35.
- Author
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Feng, Weixi, Zhang, Yanli, Ding, Shixin, Chen, Sijia, Wang, Tianqi, Wang, Ze, Zou, Ying, Sheng, Chengyu, Chen, Yan, Pang, Yingting, Marshall, Charles, Shi, Jingping, Nedergaard, Maiken, Li, Qian, and Xiao, Ming
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ALZHEIMER'S disease , *B cells , *NEUROLOGICAL disorders , *FRONTAL lobe , *MEMORY disorders - Abstract
[Display omitted] • Depletion of mature B cells aggravated Aβ load and memory deficits of 5xFAD mice. • B lymphocytes-derived interleukin-35 ameliorates Alzheimer's disease-like neuropathology. • Interleukin-35 inhibited neuronal β-site APP-cleaving enzyme 1 expression via SOCS1/STAT1 pathway. Increasing evidence supports the involvement of the peripheral immune system in the pathogenesis of Alzheimer's disease (AD). In the present study, we found that B lymphocytes could mitigate beta-Amyloid (Aβ) pathology and memory impairments in a transgenic AD mouse model. Specifically, in young 5 × FAD mice, we evidenced increased B cells in the frontal cortex and meningeal tissues; depletion of mature B cells aggravated these mice's Aβ load and memory deficits. The increased B cells produced more interleukin-35 (IL-35) in the front cortex. We further found IL-35 neutralization exacerbated Aβ pathology, while injecting IL-35 mitigated Aβ load and cognitive dysfunction in 5 × FAD mice with or without mature B cell deficiency. Mechanistically, IL-35 inhibited neuronal BACE1 transcription through modulating the SOCS1/STAT1 pathway, and reduced Aβ production accordingly. Reanalysis of the single-cell RNA sequencing data from blood samples of AD patients suggested an increased population of IL-35-producing B cells. Together, the present study revealed a novel effect of B lymphocyte-derived IL-35 on inhibiting Aβ production in the frontal cortex, which may serve as a potential target for future AD treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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