Researchers will work to determine whether a specific type of innate immune cell, called a monocyte, and dendritic cell (DC) are involved in initiating inflammatory disease in the brains of laboratory animals.

Inflammation in the central nervous system (CNS, brain, and spinal cord) characterizes a number of diseases, including degenerative Parkinson’s and Alzheimer’s diseases, and autoimmune multiple sclerosis (MS), in which immune cells mistakenly attack the CNS. The researchers hypothesize that innate immune cells are recruited into the CNS in response to trauma, infection, or as a consequence of inappropriate (autoimmune) responses against the CNS. These immune cells, they further hypothesize, produce inflammatory substances that affect the function and viability of neurons and their supportive cells (glia), leading to varying degrees of neurological damage. 

The goal of this proposal is to advance our understanding of two key aspects of neuroinflammation: the mechanisms of cell recruitment, and the production of specific molecular effectors. They will determine whether the chemokine CCL2 and its receptor, CCR2, cause the influx of innate immune cells into the CNS, and they will determine whether monocytes and/or DCs, once recruited into the CNS by this chemokine, induce inflammatory CNS disease.

Significance: Determining how inflammatory diseases are induced in the CNS may lead to novel therapies to prevent these disease.