LRRK2 levels in immune cells are increased in Parkinson’s disease

D. A. Cook, G. T. Kannarkat, A. F. Cintron, Laura M. Butkovich, Kyle B. Fraser, J. Chang, N. Grigoryan, S. A. Factor, Andrew B. West, J. M. Boss, M. G. Tansey

Research output: Contribution to journalArticle

Abstract

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.
Original languageEnglish
Pages (from-to)11
Number of pages1
JournalParkinson's Disease
Volume3
Issue number1
DOIs
Publication statusPublished - 2017 Dec 28

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Leucine
Parkinson Disease
Phosphotransferases
T-Lymphocytes
Cytokines
Monocytes
Healthy Volunteers
NFATC Transcription Factors
Immunophenotyping
Immune System Diseases
T-Lymphocyte Subsets
Cytotoxic T-Lymphocytes
Immunoassay
Blood Cells
Flow Cytometry
Membrane Proteins
B-Lymphocytes
Mutation

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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. Parkinson's Disease, 3(1), 11. https://doi.org/10.1038/s41531-017-0010-8
Cook, D. A. ; Kannarkat, G. T. ; Cintron, A. F. ; Butkovich, Laura M. ; Fraser, Kyle B. ; Chang, J. ; Grigoryan, N. ; Factor, S. A. ; West, Andrew B. ; Boss, J. M. ; Tansey, M. G. / LRRK2 levels in immune cells are increased in Parkinson’s disease. In: Parkinson's Disease. 2017 ; Vol. 3, No. 1. pp. 11.
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Cook, DA, Kannarkat, GT, Cintron, AF, Butkovich, LM, Fraser, KB, Chang, J, Grigoryan, N, Factor, SA, West, AB, Boss, JM & Tansey, MG 2017, 'LRRK2 levels in immune cells are increased in Parkinson’s disease', Parkinson's Disease, vol. 3, no. 1, pp. 11. https://doi.org/10.1038/s41531-017-0010-8

LRRK2 levels in immune cells are increased in Parkinson’s disease. / Cook, D. A.; Kannarkat, G. T.; Cintron, A. F.; Butkovich, Laura M.; Fraser, Kyle B.; Chang, J.; Grigoryan, N.; Factor, S. A.; West, Andrew B.; Boss, J. M.; Tansey, M. G.

In: Parkinson's Disease, Vol. 3, No. 1, 28.12.2017, p. 11.

Research output: Contribution to journalArticle

TY - JOUR

T1 - LRRK2 levels in immune cells are increased in Parkinson’s disease

AU - Cook, D. A.

AU - Kannarkat, G. T.

AU - Cintron, A. F.

AU - Butkovich, Laura M.

AU - Fraser, Kyle B.

AU - Chang, J.

AU - Grigoryan, N.

AU - Factor, S. A.

AU - West, Andrew B.

AU - Boss, J. M.

AU - Tansey, M. G.

PY - 2017/12/28

Y1 - 2017/12/28

N2 - 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.

AB - 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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DO - 10.1038/s41531-017-0010-8

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JO - Parkinson's Disease

JF - Parkinson's Disease

SN - 2090-8083

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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. Parkinson's Disease. 2017 Dec 28;3(1):11. https://doi.org/10.1038/s41531-017-0010-8