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<p>Parkinson’s disease is characterized by a period of non-motor symptoms, including gastrointestinal dysfunction, preceding motor deficits by several years to decades. This long prodrome is suggestive of peripheral immunity involvement in the initiation of disease. We previously developed a model system in PINK1 KO mice displaying PD-like motor symptoms at late stages following intestinal infections. Herein, we map the initiating immune events at the site of infection in this model. Using single-cell RNAseq, we demonstrate that peripheral myeloid cells are the earliest highly dysregulated immune cell type followed by an aberrant T cell response shortly after. We also demonstrate an increased propensity for antigen presentation and that activated myeloid cells acquire a proinflammatory profile capable of inducing cytotoxic T cell responses. Together, our study provides the first evidence that PINK1 is a key regulator of immune functions in the gut underlying early PD-related disease mechanisms.</p>

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PINK1 deficiency rewires early immune responses in a mouse model of Parkinson’s disease triggered by intestinal infection

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月22日

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  • Sherilyn Junelle Recinto,
  • Alexandra Kazanova,
  • Lin Liu,
  • Brendan Cordeiro,
  • Shobina Premachandran,
  • Hicham Bessaiah,
  • Alexis Allot,
  • Elia Afanasiev,
  • Sriparna Mukherjee,
  • Jessica Pei,
  • Adam MacDonald,
  • Moein Yaqubi,
  • Heidi M. McBride,
  • Diana Matheoud,
  • Louis-Eric Trudeau,
  • Samantha Gruenheid,
  • Jo Anne Stratton

摘要

Parkinson’s disease is characterized by a period of non-motor symptoms, including gastrointestinal dysfunction, preceding motor deficits by several years to decades. This long prodrome is suggestive of peripheral immunity involvement in the initiation of disease. We previously developed a model system in PINK1 KO mice displaying PD-like motor symptoms at late stages following intestinal infections. Herein, we map the initiating immune events at the site of infection in this model. Using single-cell RNAseq, we demonstrate that peripheral myeloid cells are the earliest highly dysregulated immune cell type followed by an aberrant T cell response shortly after. We also demonstrate an increased propensity for antigen presentation and that activated myeloid cells acquire a proinflammatory profile capable of inducing cytotoxic T cell responses. Together, our study provides the first evidence that PINK1 is a key regulator of immune functions in the gut underlying early PD-related disease mechanisms.