Pulmonary B cells ameliorate Alzheimer's disease-like neuropathology
Feng, W.; Zhang, Y.; Wang, T.; Wang, Z.; Chen, Y.; Sheng, C.; Zou, Y.; Pang, Y.; Gao, J.; Zhang, Y.; Shi, J.; Li, Q.; Xiao, M.
Show abstract
Increasing evidence shows that the peripheral immune system is involved in the pathogenesis of Alzheimers disease (AD). Here, we report that pulmonary B cells mitigate beta-Amyloid (A{beta}) pathology in 5xFAD mice. The proportion of B cells rather than T cells increases in brain, meningeal and lung tissues in 3-month-old 5xFAD mice. Deletion of B cells aggravates A{beta} load and memory deficits of 5xFAD mice. Mechanimsly, pulmonary B cells can migrate to the brain parenchyma and produce interleukin-35 that inhibits neuronal {beta}-site APP-cleaving enzyme 1 expression, subsequently reducing the production of A{beta}. In turn, proliferation of pulmonary B cells is associated with activation of toll-like receptor/nuclear factor kappa-B pathway by elevated A{beta} that is drained from the brain parenchyma to the lungs via meningeal lymphatics. Furthermore, promoting pulmonary B cell proliferation via overexpression of B-cell-activating factor ameliorates brain A{beta} load and improves cognitive functions of 10-month-old 5xFAD mice. Together, these results highlight the lungs as both immune targets and effector organs in A{beta} pathogenesis. Pulmonary B cells might be a potential target against AD.
Matching journals
The top 10 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Microglia and border-associated mouse macrophages maintain their embryonic origin during Alzheimers disease 94%
- Downregulation of Dickkopf-3, a Wnt antagonist elevated in Alzheimer's disease, restores synapse integrity and memory in a disease mouse model 94%
- Molecular and cellular similarities in the brain of SARS-CoV-2 and Alzheimer's disease individuals 93%
Similar papers in this journal
- Identification of Chlamydia pneumoniae and NLRP3 inflammasome activation in Alzheimer's disease retina 94%
- Microglial NF-κB drives tau spreading and toxicity in a mouse model of tauopathy 93%
- Novel brain-penetrant inhibitor of G9a methylase blocks Alzheimer’s disease proteopathology for precision medication 93%
Similar papers in this journal
- A Trem2*R47H mouse model without cryptic splicing drives age- and disease-dependent tissue damage and synaptic loss in response to plaques 94%
- APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology 94%
- TREM2-H157Y Increases Soluble TREM2 Production and Reduces Amyloid Pathology 94%
Similar papers in this journal
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.