Sommer, Annika and Maxreiter, Franz and Krach, Florian and Fadler, Tanja and Grosch, Janina and Maroni, Michele and Graef, Daniela and Eberhardt, Esther and Riemenschneider, Markus J. and Yeo, Gene W. and Kohl, Zacharias and Xiang, Wei and Gage, Fred H. and Winkler, Juergen and Prots, Iryna and Winner, Beate (2018) Th17 Lymphocytes Induce Neuronal Cell Death in a Human iPSC-Based Model of Parkinson's Disease. CELL STEM CELL, 23 (1). 123-+. ISSN 1934-5909, 1875-9777
Full text not available from this repository. (Request a copy)Abstract
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 NF kappa B 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PLURIPOTENT STEM-CELLS; T-CELLS; NEURODEGENERATION; NEUROINFLAMMATION; CONTRIBUTES; POPULATIONS; DYSFUNCTION; MICROGLIA; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Neuropathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 04 Mar 2020 08:33 |
| Last Modified: | 04 Mar 2020 08:33 |
| URI: | https://pred.uni-regensburg.de/id/eprint/14254 |
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