Peripheral CD4+ T lymphocyte subsets exhibit functional alterations in Parkinson's disease, influencing neuroinflammation.

Parkinson disease (PD) is a prevalent neurodegenerative disorder in the elderly, characterized by progressive neuronal loss. A critical driver of this neurodegeneration is neuroinflammation, which is significantly influenced by the peripheral adaptive immune system. Current treatments primarily manage symptoms, but disease-modifying therapies targeting the underlying neuroinflammatory processes are lacking. This review addresses the gap in understanding how specific peripheral immune cells, particularly CD4+ T lymphocyte subsets, contribute to and regulate neuroinflammation in PD.

This review systematically analyzed existing literature to discuss the regulatory roles of neuroinflammation by CD4+ T cell subsets (T helper [Th] cell 1, Th2, Th17, Th9, and regulatory T cells) in Parkinson disease. The authors emphasized the specific roles and mechanisms of these CD4+ T cell subsets, along with the cytokines they secrete, in PD pathogenesis. They explored the associations between helper T cells, regulatory T cells, and core cytokines (interleukin 2, 6, 8, tumor necrosis factor-α, interferon-γ), as well as chemokines (monocyte chemoattractant protein-1), with PD progression. The ultimate goal was to clarify the contribution of peripheral inflammation to disease progression and identify potential therapeutic targets.

The review synthesizes evidence indicating that specific CD4+ T cell subsets and their secreted cytokines play crucial regulatory roles in Parkinson disease neuroinflammation. It details how Th1, Th2, Th17, Th9, and Treg cells are functionally altered in PD patients, influencing the inflammatory milieu. The review highlights that core cytokines such as IL-2, IL-6, IL-8, TNF-α, and IFN-γ, along with the chemokine MCP-1, are significantly associated with disease progression, reflecting the active involvement of peripheral immunity. > The review clarified that peripheral inflammation, mediated by these CD4+ T cell subsets, significantly contributes to the neurodegenerative processes observed in Parkinson disease, suggesting a direct link between systemic immune dysregulation and central nervous system pathology. This comprehensive analysis of CD4+ T cell subset operation within the nervous system provides a foundation for developing new therapeutic interventions.