Th17 cells: a promising therapeutic target for Parkinson’s disease?

ABSTRACT

Introduction: Parkinson’s disease (PD) is the most common neurodegenerative movement disorder caused by the progressive loss of neurons in the midbrain and other brain regions. Only symptomatic treatment is currently available. Mounting evidence suggests that T cells are a key contributor to PD pathogenesis and neurodegeneration by a mechanism that requires further elucidation.

Areas covered: We discuss the evidence of imbalanced activation of effector T cell populations in PD and summarize the data of Th17 involvement and Th17-regulated mechanisms in PD pathology. Moreover, possible Th17-related molecular targets as possible neuroprotective immunomodulatory therapeutic targets for PD are examined.

Expert Opinion: Existing data show that Th17 cells, their effector molecules, and signaling pathways are potentially effective therapeutic targets for neuroprotective immunomodulation in PD treatment. However, specificity of action within Th17-mediated signaling pathways for PD requires careful consideration.

KEYWORDS:

• IL-1β
• IL-6
• neurodegeneration
• Parkinson’s disease
• T cells
• Th17 cells

Article highlights

• T cells are involved in the pathogenesis of Parkinson’s disease (PD).

• An imbalance between pro-inflammatory Th17 cells and anti-inflammatory Treg cells may exist in PD.

• Th17 cells are increased in the blood of PD patients and are promoted by the pro-inflammatory cytokines IL-1β and IL-6, which are increased in PD serum and brain.

• Th17 cells can induce neurotoxicity in PD models via IL-17/IL-17R or LFA-1/ICAM-1 systems.

Th17 developmental pathways and their effector mechanisms might represent promising therapeutic strategies for PD.

This box summarizes key points contained in the article.

Acknowledgments

We are thankful to all patients and controls who participated in the referred studies.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the German Federal Ministry of Education and Research (BMBF) under Grant [number 01EK1609B] and by the Deutsche Forschungsgemeinschaft (DFG) funded research training group GRK 2162.