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bioRxiv · 10.1101/2020.11.23.393942

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.·Shi, J.·Li, Q.·Xiao, M.
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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.

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Feng, W., Zhang, Y., Wang, T., Wang, Z., Chen, Y., Sheng, C., Zou, Y., Pang, Y., Gao, J., Shi, J., Li, Q., Xiao, M.. 2020-11-23. Pulmonary B cells ameliorate Alzheimer's disease-like neuropathology. https://doi.org/10.1101/2020.11.23.393942

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