Th17 Lymphocytes Induce Neuronal Cell Death in a Human iPSC-Based Model of Parkinson’s Disease

Publication date: 5 July 2018

Source: Cell Stem Cell, Volume 23, Issue 1

Author(s): Annika Sommer, Franz Maxreiter, Florian Krach, Tanja Fadler, Janina Grosch, Michele Maroni, Daniela Graef, Esther Eberhardt, Markus J. Riemenschneider, Gene W. Yeo, Zacharias Kohl, Wei Xiang, Fred H. Gage, Jürgen Winkler, Iryna Prots, Beate Winner

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.

Graphical Abstract

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