The development and function of aging-associate innate lymphoid cells in the choroid plexus

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Project Summary/Abstract The goal of this project is to understand the development and function of aging-associate lymphocytes. This proposal focuses on group 2 innate lymphoid cells (ILC2) that accumulate in the choroid plexus (CP) with aging. Aging is a complicated process associated with profound changes in the immune system, characterized by both a deterioration of adaptive immune function (immunosenescence) and also increased inflammation (inflammaging). Suprisingly, some immune cell subsets with anti-inflammatory and reparative function also accumulate with aging, which might represent a protective negative feedback mechanism to counter inflammaging. Our recent work discovers that group-2 innate lymphoid cells (ILC2), a type of tissue-resident innate lymphocytes, accumulate in the CP of aged mice and humans. The goal of this proposal is to understand the development and function of these aging-associated innate lymphoid cells in the CP. We will use lineage tracking mice, precursor homing assay, and adoptive transfer to examine the developmental origins of these cells and to explore the factors that lead to their accumulation with aging. We will use ILC2 deficient and ILC2 inducible-deletion mice to examine the specific role of these cells in physiological aging. Finally, we will test whether enhancing ILC2 function can alleviate neuroinflammation and cognitive impairment in aged mice with Alzheimer’s disease associated pathologies. We expect that the data generated will provide significant insights into the mechanisms of immune cell aging, and will inform strategies to combat geriatric diseases.