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LRRK2 levels in immune cells are increased in Parkinson's disease.

Publication ,  Journal Article
Cook, DA; Kannarkat, GT; Cintron, AF; Butkovich, LM; Fraser, KB; Chang, J; Grigoryan, N; Factor, SA; West, AB; Boss, JM; Tansey, MG
Published in: NPJ Parkinsons Dis
2017

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.

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Published In

NPJ Parkinsons Dis

DOI

ISSN

2373-8057

Publication Date

2017

Volume

3

Start / End Page

11

Location

United States

Related Subject Headings

  • 5204 Cognitive and computational psychology
  • 5202 Biological psychology
  • 3209 Neurosciences
 

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ICMJE
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Cook, D. A., Kannarkat, G. T., Cintron, A. F., Butkovich, L. M., Fraser, K. B., Chang, J., … Tansey, M. G. (2017). LRRK2 levels in immune cells are increased in Parkinson's disease. NPJ Parkinsons Dis, 3, 11. https://doi.org/10.1038/s41531-017-0010-8
Cook, D. A., G. T. Kannarkat, A. F. Cintron, Laura M. Butkovich, Kyle B. Fraser, J. Chang, N. Grigoryan, et al. “LRRK2 levels in immune cells are increased in Parkinson's disease.NPJ Parkinsons Dis 3 (2017): 11. https://doi.org/10.1038/s41531-017-0010-8.
Cook DA, Kannarkat GT, Cintron AF, Butkovich LM, Fraser KB, Chang J, et al. LRRK2 levels in immune cells are increased in Parkinson's disease. NPJ Parkinsons Dis. 2017;3:11.
Cook, D. A., et al. “LRRK2 levels in immune cells are increased in Parkinson's disease.NPJ Parkinsons Dis, vol. 3, 2017, p. 11. Pubmed, doi:10.1038/s41531-017-0010-8.
Cook DA, Kannarkat GT, Cintron AF, Butkovich LM, Fraser KB, Chang J, Grigoryan N, Factor SA, West AB, Boss JM, Tansey MG. LRRK2 levels in immune cells are increased in Parkinson's disease. NPJ Parkinsons Dis. 2017;3:11.

Published In

NPJ Parkinsons Dis

DOI

ISSN

2373-8057

Publication Date

2017

Volume

3

Start / End Page

11

Location

United States

Related Subject Headings

  • 5204 Cognitive and computational psychology
  • 5202 Biological psychology
  • 3209 Neurosciences