DAT and TH expressing myeloid-derived suppressor cells are increased in Parkinson's Disease
Basil Hashimi and Martin Badov
Authors: Basil Hashimi, Adithya Gopinath, Martin Badov, Madison Francis, Michael Okun, Wolfgang J. Streit, Habibeh Khoshboeui
Faculty Mentor: Habibeh Khoshboeui
College: College of Medicine
Parkinson’s disease (PD) is characterized by dopaminergic degeneration and is thought to start in the periphery. The nature of communication between the periphery and central nervous system (CNS) remains unclear. Peripheral immune cells express key dopaminergic proteins, including dopamine transporter (DAT) and tyrosine hydroxylase (TH), and may be regulated by CNS-produced dopamine. After establishing a novel flow cytometry protocol to detect DAT, TH, and CD14 expression in the monocytes of PD patients, we made the surprising discovery of increased DAT/TH+ and CD14+ monocytes in PD patients versus healthy controls. We next hypothesized that the CD14+ monocyte population in PD patients is composed of multiple subsets of monocytes, including myeloid-derived suppressor cells (MDSCs), capable of altering the immune landscape through infiltration. Extensive characterization of the altered monocyte population revealed that CD14+ HLA-DR(-) monocytes, defined as monocytic-MDSCs, are significantly elevated in PD patients. This population, capable of inhibiting immune function of other immune cells system wide, supports the interpretation that there are specific monocyte populations which could be involved in the mechanistic relationship between the peripheral immune system and changes in CNS dopamine in PD.
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