alexa Tyrosine Kinase Inhibition Regulates Early Systemic Immune Changes and Modulates the Neuroimmune Response in α-Synucleinopathy
ISSN: 2155-9899

Journal of Clinical & Cellular Immunology
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Research Article

Tyrosine Kinase Inhibition Regulates Early Systemic Immune Changes and Modulates the Neuroimmune Response in α-Synucleinopathy

Michaeline L. Hebron1, Irina Lonskaya1, Paul Olopade1, Sandra T. Selby2, Fernando Pagan3 and Charbel E-H Moussa1,3*
1Department of Neuroscience, Laboratory for Dementia and Parkinsonism, Georgetown University Medical Center, Washington D.C., 20007, USA
2Department of Oncology, Lombardi Cancer Center, Georgetown University Medical Center, Washington D.C., 20007, USA
3Neurorestoration Group, Movement Disorders Program, National Parkinson Foundation Center of Excellence, Georgetown University Medical Center, Washington D.C., 20007, USA
Corresponding Author : Charbel E-H. Moussa, MB. Ph.D.
Department of Neuroscience
Georgetown University School of Medicine
3970 Reservoir Rd, NW, TRB
Room WP09B, Washington DC 20057, USA
Tel: 202-687-7328
Fax: 202-687-0617
Received August 12, 2014; Accepted September 23, 2014; Published September 30, 2014
Citation: Hebron ML, Lonskaya I, Olopade P, Selby ST, Pagan F, et al. (2014) Tyrosine Kinase Inhibition Regulates Early Systemic Immune Changes and Modulates the Neuroimmune Response in α-Synucleinopathy. J Clin Cell Immunol 5:259. doi:10.4172/2155-9899.1000259
Copyright: © 2014 Hebron ML, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Objectives: Neuro-inflammation is common in α-Synucleinopathies and Tauopathies; and evidence suggests a link between the tyrosine kinase Abl and neurodegeneration. Abl upregulates α-Synuclein and promotes Tau hyper-phosphorylation (p-Tau), while Abl inhibitors facilitate autophagic clearance.

Methods: A model of α-Synucleinopathy harboring human mutant A53T α-Synuclein and exhibits concomitant increase in murine p-Tau was used to determine the immunological response to Abl inhibition.

Results: Age-dependent alterations of brain immunity, including loss of IL-10 and decreased levels of IL-2 and IL-3 were observed in old A53T mice. Brain CCL2 and CCL5 were decreased, but CX3CL1 remained constantly elevated. Young A53T mice exhibited differential systemic and central immune profiles in parallel with increased blood markers of adaptive immunity, suggesting an early systemic immune response. Tyrosine kinase inhibitors (TKIs), including nilotinib and bosutinib reduced brain and peripheral α-Synuclein and p-Tau and modulated blood immunological responses. TKIs did not affect brain IL-10, but they changed the levels of all measured blood immune markers, except CX3CL1. TKIs altered microglia morphology and reduced the number of astrocyte and dendritic cells, suggesting beneficial regulation of microglia.

Conclusions: These data indicate that tyrosine kinase inhibition affects neuro-inflammation via early changes of peripheral immune profile, leading to modulation of neuro-immune response to α-Synuclein and p-Tau.


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