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

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          Abstract

          <p class="first" id="d3309849e249">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. </p>

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          Author and article information

          Journal
          Cell Stem Cell
          Cell Stem Cell
          Elsevier BV
          19345909
          July 2018
          July 2018
          : 23
          : 1
          : 123-131.e6
          Article
          10.1016/j.stem.2018.06.015
          29979986
          cbd11e3e-2aeb-445d-a5be-60e0546a4912
          © 2018

          https://www.elsevier.com/tdm/userlicense/1.0/

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