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

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autor(en): 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
Zeitschrift: Cell Stem Cell
Jahr der Veröffentlichung: 2018
Band: 23
Heftnummer: 1
Seitenbereich: 123-+
ISSN: 1934-5909


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.


FAU-Autoren / FAU-Herausgeber

Eberhardt, Esther Dr. med.
Medizinische Fakultät
Fadler, Tanja
Lehrstuhl für Biochemie und Pathobiochemie
Grosch, Janina
Professur für Molekulare Neurologie
Kohl, Zacharias PD Dr.
Molekular-Neurologische Abteilung in der Neurologischen Klinik
Maroni, Michele
Anästhesiologische Klinik
Prots, Iryna Dr.
Professur für Stammzell-Modelle seltener neuraler Erkrankungen
Sommer, Annika
Klinisch-Molekularbiologisches Forschungszentrum
Winkler, Jürgen Prof. Dr.
Molekular-Neurologische Abteilung in der Neurologischen Klinik
Winner, Beate Prof. Dr.
Professur für Stammzell-Modelle seltener neuraler Erkrankungen
Xiang, Wei PD Dr.
Lehrstuhl für Biochemie und Molekulare Medizin


Autor(en) der externen Einrichtung(en)
Salk Institute for Biological Studies
Universitätsklinikum Regensburg
University of California, San Diego


Zitierweisen

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-+.

BibTeX: 

Zuletzt aktualisiert 2019-25-03 um 10:53