Research
The Neuroimmunology Initiative encompasses three interconnected research programs to advance our understanding of the inflammatory processes and crosstalk between nervous and immune systems associated with aging and diseases, such as Alzheimer’s disease, multiple sclerosis, long COVID, and cancer.
RESEARCH PROGRAM 1
Body to Brain: Impact of peripheral inflammation on brain cell function
In this line of research, our team will determine how different types of inflammatory events originating in the periphery—such as viral infection, aging, and cancer—impact different brain cell types and regions. Additionally, we will investigate the extent to which immune cells, such as T cells, infiltrate the brain and the spinal cord following infections caused by various pathogens. This research program will provide, for the first time, (1) a spatial map of how the nervous system reacts to particular types of inflammation and cytokines, (2) the brain regions in which immune cells infiltrate and establish long-term residency after infection, and (3) the extent to which recurrent infections induce long-lasting changes in the brain’s cellular composition and foster “inflammatory memory” through the induction of epigenetic alterations in neurons and glial cells.
RESEARCH PROGRAM 2
Within the Brain: Impact of immune signaling on brain resident cells
This line of investigation will unravel how resident brain cells, namely microglia, astrocytes, and neurons, interact and influence each other during inflammatory events. We will assess how this cellular crosstalk impacts brain inflammation, function, and cognitive performance. We will also investigate how the immune cells that infiltrate the nervous system in response to peripheral infection interact with and impact resident brain cells and alter the inflammatory milieu and cerebrospinal fluid in the brain. Finally, we will selectively deplete specific immune cell subsets, such as memory T cells, to delineate their contribution to sustaining brain inflammation over time. Through this multifaceted approach, this third research program aims to provide insights into the intricate dynamics between infection, immune response, and brain homeostasis. Moreover, it may unveil therapeutic targets to mitigate chronic brain inflammation, which is associated with aging and neurodegenerative diseases such as AD.
RESEARCH PROGRAM 3
Brain to Body: Impact of neural signaling on peripheral immunity
This research will look at the flip side of the coin: how the nervous system (brain and spinal cord) senses and influences inflammation and immune responses elsewhere in the body. We will first use neural tracing techniques to identify specific cell types in the brain and spinal cord that respond to inflammatory events such as infection or cancer. This will identify the neurons that relay the health status of an organ or tissue to the nervous system. We will then use genetic and pharmacological manipulations to investigate the roles of those neurons in modulating the immune responses. We will also activate different stress pathways (e.g., such as those regulating depression and chronic stress) in the brain and spinal cord to see whether an individual’s mental state impacts immune responses. This second research program will construct a road map of neuronal circuits and interoceptive signals that distinguish between different types of immune responses occurring in different organs. Additionally, it will begin to deduce how different types of neuronal stress responses impact the initiation and resolution of immune responses in the periphery.
Together, these three synergistic research programs will illuminate novel therapeutic targets to mitigate, halt, or reverse the adverse impact of inflammation on brain health and function, thereby enhancing patient outcomes.