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

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2020 Jun 7

PMID 32503894

Citations 46

Authors

Yuanyue Zhang

Ivan Ting Hin Fung

Poornima Sankar

Xiangyu Chen

Lisa S Robison

Longyun Ye

Shanti S DSouza

Abigail E Salinero

Marcy L Kuentzel

Sridar V Chittur

Wenzheng Zhang

Kristen L Zuloaga

Qi Yang

Affiliations

Soon will be listed here.

Abstract

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 β 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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