Abstract
Abstract Aging affects immunologic responses by a global suppression of the immune system, including dysregulation of cytokine mediators, leading to increased inflammation throughout all systems, termed inflammaging. However, understanding mechanisms of healthy aging can bypass this effect. Inflammaging also leads to poor outcomes during brain injury, making immune-targeting therapeutics tantamount to overall brain health and longevity. Two candidate immune cells microglia and group 2 innate lymphoid cells (ILC2s) may control immune responses in the aged brain Therefore, we hypothesized that ILC2s are the brains’ gatekeepers of microglia polarization to a reparative, M2-like phenotype under: (1) homeostatic conditions and (2) with aging. To address this, we used flow cytometry to quantify ILC2s between young and aged male and female C57Bl6/J mice, showing an age-related increase in aged males. Moreover, when we stimulated ILC2s, the data indicated an age-related increase in cytokine production in males. We also utilized conditioned media transfer experiments from stimulated young and aged ILC2s to quiescent microglia and assessed their morphologic, genomic, proteomic, and functional changes using microscopy, qRT-PCR, Western immunoblotting, and phagocytosis assays. We showed more complex microglia morphology (indicating microglial priming) and an increase in reparative mRNA, proteins, and phagocytic function in microglia, which was augmented by aged ILC2s. Taken together, we have defined the capacity of ILC2 soluble factors to polarize microglia to a reparative phenotype and maintain this in aging. Supported by the NIH NINDS F31NS118983
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call