%0 Journal Article
%T LRRK2 levels in immune cells are increased in Parkinson¡¯s disease
%A A. F. Cintron
%A Andrew B. West
%A D. A. Cook
%A G. T. Kannarkat
%A J. Chang
%A J. M. Boss
%A Kyle B. Fraser
%A Laura M. Butkovich
%A M. G. Tansey
%A N. Grigoryan
%A S. A. Factor
%J Archive of "NPJ Parkinson's Disease".
%D 2017
%R 10.1038/s41531-017-0010-8
%X Mutations associated with leucine-rich repeat kinase 2 are the most common known cause of Parkinson¡¯s disease. The known expression of leucine-rich repeat kinase 2 in immune cells and its negative regulatory function of nuclear factor of activated T cells implicates leucine-rich repeat kinase 2 in the development of the inflammatory environment characteristic of Parkinson¡¯s disease. The aim of this study was to determine the expression pattern of leucine-rich repeat kinase 2 in immune cell subsets and correlate it with the immunophenotype of cells from Parkinson¡¯s disease and healthy subjects. For immunophenotyping, blood cells from 40 Parkinson¡¯s disease patients and 32 age and environment matched-healthy control subjects were analyzed by flow cytometry. Multiplexed immunoassays were used to measure cytokine output of stimulated cells. Leucine-rich repeat kinase 2 expression was increased in B cells (p£¿=£¿0.0095), T cells (p£¿=£¿0.029), and CD16+ monocytes (p£¿=£¿0.01) of Parkinson¡¯s disease patients compared to healthy controls. Leucine-rich repeat kinase 2 induction was also increased in monocytes and dividing T cells in Parkinson¡¯s disease patients compared to healthy controls. In addition, Parkinson¡¯s disease patient monocytes secreted more inflammatory cytokines compared to healthy control, and cytokine expression positively correlated with leucine-rich repeat kinase 2 expression in T cells from Parkinson¡¯s disease but not healthy controls. Finally, the regulatory surface protein that limits T-cell activation signals, CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), was decreased in Parkinson¡¯s disease compared to HC in T cells (p£¿=£¿0.029). In sum, these findings suggest that leucine-rich repeat kinase 2 has a regulatory role in immune cells and Parkinson¡¯s disease. Functionally, the positive correlations between leucine-rich repeat kinase 2 expression levels in T-cell subsets, cytokine expression and secretion, and T-cell activation states suggest that targeting leucine-rich repeat kinase 2 with therapeutic interventions could have direct effects on immune cell function
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5459798/