| First Author | Feng W | Year | 2023 |
| Journal | Brain Behav Immun | Volume | 108 |
| Pages | 16-31 | PubMed ID | 36427805 |
| Mgi Jnum | J:344587 | Mgi Id | MGI:7432113 |
| Doi | 10.1016/j.bbi.2022.11.012 | Citation | Feng W, et al. (2023) B lymphocytes ameliorate Alzheimer's disease-like neuropathology via interleukin-35. Brain Behav Immun 108:16-31 |
| abstractText | 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 (Abeta) pathology and memory impairments in a transgenic AD mouse model. Specifically, in young 5 x FAD mice, we evidenced increased B cells in the frontal cortex and meningeal tissues; depletion of mature B cells aggravated these mice's Abeta 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 Abeta pathology, while injecting IL-35 mitigated Abeta load and cognitive dysfunction in 5 x FAD mice with or without mature B cell deficiency. Mechanistically, IL-35 inhibited neuronal BACE1 transcription through modulating the SOCS1/STAT1 pathway, and reduced Abeta 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 Abeta production in the frontal cortex, which may serve as a potential target for future AD treatment. |
