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Publication : Depletion of NK Cells Improves Cognitive Function in the Alzheimer Disease Mouse Model.

First Author  Zhang Y Year  2020
Journal  J Immunol Volume  205
Issue  2 Pages  502-510
PubMed ID  32503894 Mgi Jnum  J:294337
Mgi Id  MGI:6445276 Doi  10.4049/jimmunol.2000037
Citation  Zhang Y, et al. (2020) Depletion of NK Cells Improves Cognitive Function in the Alzheimer Disease Mouse Model. J Immunol 205(2):502-510
abstractText  Despite mounting evidence suggesting the involvement of the immune system in regulating brain function, the specific role of immune and inflammatory cells in neurodegenerative diseases remain poorly understood. In this study, we report that depletion of NK cells, a type of innate lymphocytes, alleviates neuroinflammation, stimulates neurogenesis, and improves cognitive function in a triple-transgenic Alzheimer disease (AD) mouse model. NK cells in the brains of triple-transgenic AD mouse model (3xTg-AD) mice exhibited an enhanced proinflammatory profile. Depletion of NK cells by anti-NK1.1 Abs drastically improved cognitive function of 3xTg-AD mice. NK cell depletion did not affect amyloid beta concentrations but enhanced neurogenesis and reduced neuroinflammation. Notably, in 3xTg-AD mice depleted of NK cells, microglia demonstrated a homeostatic-like morphology, decreased proliferative response and reduced expression of neurodestructive proinflammatory cytokines. Together, our results suggest a proinflammatory role for NK cells in 3xTg-AD mice and indicate that targeting NK cells might unlock novel strategies to combat AD.
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