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

Sommer A, Maxreiter F, Krach F, Fadler T, Grosch J, Maroni M, Graef D, Eberhardt E, Riemenschneider MJ, Yeo GW, Kohl Z, Xiang W, Gage FH, Winkler J, Prots I, Winner B (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Cell Stem Cell Elsevier (Cell Press)

Book Volume: 23

Pages Range: 123-+

Journal Issue: 1

DOI: 10.1016/j.stem.2018.06.015

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.

Authors with CRIS profile

Annika Sommer Klinisch-Molekularbiologisches Forschungszentrum Tanja Fadler Lehrstuhl für Biochemie und Pathobiochemie Janina Grosch Professur für Molekulare Neurologie Michele Maroni Department of Anaesthesiology Esther Eberhardt Medizinische Fakultät Zacharias Kohl Department of Molecular Neurology Wei Xiang Lehrstuhl für Biochemie und Molekulare Medizin Jürgen Winkler Professur für Molekulare Neurologie Iryna Prots Professur für Stammzell-Modelle seltener neuraler Erkrankungen Beate Winner Professur für Stammzell-Modelle seltener neuraler Erkrankungen

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Related research project(s)

IZKF-J66 (AN): ß subunits in human stem cell-derived nociceptors - adding pieces to the puzzle of pain Jan. 1, 2018 - Aug. 31, 2020

Involved external institutions

Salk Institute for Biological Studies US United States (USA) (US) Universitätsklinikum Regensburg DE Germany (DE) University of California, San Diego US United States (USA) (US)

How to cite

APA:

Sommer, A., Maxreiter, F., Krach, F., Fadler, T., Grosch, J., Maroni, M.,... Winner, B. (2018). Th17 Lymphocytes Induce Neuronal Cell Death in a Human iPSC-Based Model of Parkinson's Disease. Cell Stem Cell, 23(1), 123-+. https://dx.doi.org/10.1016/j.stem.2018.06.015

MLA:

Sommer, Annika, et al. "Th17 Lymphocytes Induce Neuronal Cell Death in a Human iPSC-Based Model of Parkinson's Disease." Cell Stem Cell 23.1 (2018): 123-+.

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