Abstract
BackgroundThe immune pathways in Alzheimer’s disease (AD) remain incompletely understood. Our recent study indicates that tissue-resident group 2 innate lymphoid cells (ILC2) accumulate in the brain barriers of aged mice and that their activation alleviates aging-associated cognitive decline. The regulation and function of ILC2 in AD, however, remain unknown.MethodsIn this study, we examined the numbers and functional capability of ILC2 from the triple transgenic AD mice (3xTg-AD) and control wild-type mice. We investigated the effects of treatment with IL-5, a cytokine produced by ILC2, on the cognitive function of 3xTg-AD mice.ResultsWe demonstrate that brain-associated ILC2 are numerically and functionally defective in the triple transgenic AD mouse model (3xTg-AD). The numbers of brain-associated ILC2 were greatly reduced in 7-month-old 3xTg-AD mice of both sexes, compared to those in age- and sex-matched control wild-type mice. The remaining ILC2 in 3xTg-AD mice failed to efficiently produce the type 2 cytokine IL-5 but gained the capability to express a number of proinflammatory genes. Administration of IL-5, a cytokine produced by ILC2, transiently improved spatial recognition and learning in 3xTg-AD mice.ConclusionOur results collectively indicate that numerical and functional deficiency of ILC2 might contribute to the cognitive impairment of 3xTg-AD mice.
Highlights
Alzheimer’s disease (AD) is a devastating disease that affects more than 50 million people worldwide
Group 2 innate lymphoid cells (ILC2) were enriched in the barrier tissues including choroid plexus, perivascular tissue, and leptomeninges of wild-type mice, and their numbers were reduced in age- and sex-matched 3xTg-AD mice (Fig. 1C)
Our work indicates that treatment with IL-5, a cytokine produced by ILC2, may enhance spatial recognition of 7-month-old 3xTg-AD mice
Summary
Alzheimer’s disease (AD) is a devastating disease that affects more than 50 million people worldwide. Recent studies indicate potential roles for peripheral and tissue-resident lymphocytes in regulating AD development and progression. Depletion of NK cells, the innate lymphocyte subset with cytotoxic function, alleviated neuroinflammation and cognitive decline in the triple transgenic mouse model of AD (3xTg-AD) [5]. Genetic deletion of both adaptive and innate lymphocytes led to exacerbated Aβ pathology in 5xfAD mice, indicating that some other lymphocyte subsets might instead play a protective role in AD [6]. The function and regulation of other lymphocyte subsets in AD are yet to be better understood. The immune pathways in Alzheimer’s disease (AD) remain incompletely understood. Our recent study indicates that tissue-resident group 2 innate lymphoid cells (ILC2) accumulate in the brain barriers of aged mice and that their activation alleviates aging-associated cognitive decline. The regulation and function of ILC2 in AD, remain unknown
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