Abstract
Increasing evidence supports the role of brain and systemic inflammation in the etiology of Parkinson disease (PD). We used gene expression profiling to examine the activation state of peripheral blood monocytes in 18 patients with early, untreated PD and 16 healthy control (HC) subjects. Monocytes were isolated by negative selection, and gene expression studied by RNA-seq and gene set enrichment analysis. A computational model that incorporated case/control status, sex, and the interaction between case/control status and sex was utilized. We found that there was a striking effect of sex on monocyte gene expression. There was inflammatory activation of monocytes in females with PD, with enrichment of gene sets associated with interferon gamma stimulation. In males, the activation patterns were more heterogeneous. These data point to the importance of systemic monocyte activation in PD, and the importance of studies which examine the differential effects of sex on pathophysiology of the disease.
Highlights
Recent studies have revealed a critical role for activation of the immune system in the pathogenesis of Parkinson disease (PD)[1]
There is an increase in inflammatory cytokines including IL-6 and IFN- γ5, modifications of circulating monocytes[6,7], changes in regulatory and effector Tcells[8], and induction of memory T-cells with a specific response to alpha-synuclein (α-syn)[9,10], a protein with a central role in the pathophysiology of PD
Evidence linking blood monocytes to the pathogenesis of PD includes gene expression studies, which show prominent expression of PD-associated genes in monocytes[16]; prior human studies, which have demonstrated evidence for alterations of blood monocytes in PD6; and work in animal models, which has shown that entry of monocytes from the blood into the brain is a critical step in α-syn mediated neurodegeneration[14]
Summary
Recent studies have revealed a critical role for activation of the immune system in the pathogenesis of Parkinson disease (PD)[1]. Monocytes are cells of myeloid lineage, derived from the bone marrow They are phagocytic and play a critical role in immune surveillance through engulfing, processing, and presenting foreign antigens for recognition by the adaptive arm of the immune system. Evidence linking blood monocytes to the pathogenesis of PD includes gene expression studies, which show prominent expression of PD-associated genes in monocytes[16]; prior human studies, which have demonstrated evidence for alterations of blood monocytes in PD6; and work in animal models, which has shown that entry of monocytes from the blood into the brain is a critical step in α-syn mediated neurodegeneration[14]
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