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

Cell Stem Cell. 2018 Jul 5;23(1):123-131.e6. doi: 10.1016/j.stem.2018.06.015.


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.

Keywords: Sporadic Parkinson’s disease; T lymphocytes; Th17 cells; human autologous co-culture; neuroinflammation.

MeSH terms

  • Cell Death*
  • Cells, Cultured
  • Female
  • Humans
  • Induced Pluripotent Stem Cells / pathology*
  • Male
  • Models, Biological*
  • Neurons / pathology*
  • Parkinson Disease / pathology*
  • Th17 Cells / metabolism*