[PDF][PDF] Th17 lymphocytes induce neuronal cell death in a human iPSC-based model of Parkinson's disease

A Sommer, F Marxreiter, F Krach, T Fadler, J Grosch… - Cell stem cell, 2018 - cell.com
A Sommer, F Marxreiter, F Krach, T Fadler, J Grosch, M Maroni, D Graef, E Eberhardt…
Cell stem cell, 2018cell.com
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive
degeneration of midbrain neurons (MBNs). Recent evidence suggests contribution of the
adaptive immune system in PD. Here, we show a role for human T lymphocytes as cell death
inducers of induced pluripotent stem cell (iPSC)-derived MBNs in sporadic PD. Higher Th17
frequencies were found in the blood of PD patients and increased numbers of T lymphocytes
were detected in postmortem PD brain tissues. We modeled this finding using autologous co …
Summary
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive degeneration of midbrain neurons (MBNs). Recent evidence suggests contribution of the adaptive immune system in PD. Here, we show a role for human T lymphocytes as cell death inducers of induced pluripotent stem cell (iPSC)-derived MBNs in sporadic PD. Higher Th17 frequencies were found in the blood of PD patients and increased numbers of T lymphocytes were detected in postmortem PD brain tissues. We modeled this finding using autologous co-cultures of activated T lymphocytes and iPSC-derived MBNs of sporadic PD patients and controls. After co-culture with T lymphocytes or the addition of IL-17, PD iPSC-derived MBNs underwent increased neuronal death driven by upregulation of IL-17 receptor (IL-17R) and NFκB activation. Blockage of IL-17 or IL-17R, or the addition of the FDA-approved anti-IL-17 antibody, secukinumab, rescued the neuronal death. Our findings indicate a critical role for IL-17-producing T lymphocytes in sporadic PD.
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