Clinical disability in multiple sclerosis (MS) is driven by immune cell infiltration into the CNS parenchy-ma. Understanding the mechanisms by which CNS barrier cells regulate immune cell activation and en-try during this infiltrative process may identify novel therapeutic strategies for MS and other CNS auto-immune diseases.

During CNS inflammation, immune cells traffic from the blood through a two-barrier structure termed the neurovascular unit. While many have focused on entry through the first barrier, a specialized en-dothelial wall known as the blood-brain barrier, less is known about how immune cells interact with the second barrier, a layer of endfoot processes extending from specialized cells called astrocytes, a barrier referred to as the glia limitans. In MS lesions, immune cells circulate within the space between the first and second barriers, a compartment termed the perivascular space. Within this space, immune cells interact with the astrocyte endfeet and potentially receive signals that prime them for autoimmune attack.

The Horng Laboratory is interested in identifying and characterizing the signaling pathways between astrocytes and immune cells within the perivascular spaces. We are testing the hypothesis that this cross-talk regulates immune cell function prior to CNS entry and induces functional differentiation in both cell types which contributes to both the acute phase of CNS inflammation and more chronic processes of neurodegeneration.