Journal of neuroinflammationFeb 27, 2026

Interactions between brain immune cells and T cells may promote harmful protein buildup in a Parkinson's disease mouse model

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Updated Apr 6, 2026

Abstract

The model recapitulated key features of Parkinson's disease, including motor deficits and dopaminergic neuron loss.

Parkinson's disease is associated with motor dysfunction and loss of dopamine-producing neurons in the substantia nigra.
Neuroinflammation and adaptive immunity may play a role in the progression of Parkinson's disease.
In a novel model, α-synuclein overexpression and fibril injection triggered pathological changes similar to those seen in Parkinson's disease.
T cell deficiency reduced motor deficits and neurodegeneration, and lessened microglial activation in the model.
-induced chemokine levels remained elevated even without , while pro-inflammatory cytokine levels were lower.
The interaction between T cells and microglia may exacerbate neuroinflammation and contribute to the progression of Parkinson's disease.

Simplified

UNLABELLED: Parkinson's disease (PD), the second most prevalent neurodegenerative disorder, is characterized by motor dysfunction, progressive dopaminergic (DA) neuron loss in the substantia nigra, and the pathological accumulation of α-synuclein (αSyn) aggregates within Lewy bodies. Emerging evidence suggests that neuroinflammation and adaptive immunity may contribute to PD pathogenesis. To investigate the underlying mechanisms, we adapted a PD model combining AAV-mediated αSyn overexpression with intranigral injection of αSyn fibrils, which enabled us to analyze the temporal sequence of pathological and immune responses over a defined time course. The model recapitulated key features of PD, including αSyn phosphorylation, motor deficits, and nigral DA neurodegeneration, alongside early-stage microglial activation and T cell infiltration. Furthermore, T cell deficiency markedly reduced these pathological changes and attenuated microglial activation, and pharmacological depletion of suppressed T cell accumulation in the brain and mitigated PD pathology. Notably, microglia-associated chemokine induction remained detectable despite T cell deficiency, whereas pro-inflammatory cytokine induction was attenuated, suggesting amplification of neuroinflammation through T cell–microglia interactions. These findings underscore the crucial role of T cell–microglia crosstalk in accelerating PD pathogenesis, and suggest that targeting this early immune–glial interplay may help mitigate PD-related neuroinflammation and neuronal degeneration.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-026-03734-1.

Key numbers

7.8×

Increase in T cell infiltration

Upregulation of TNF-α in infiltrating the brain after α-synuclein injection.

66.3%

Reduction in dopaminergic neuron loss

Percentage of TH-positive neurons remaining in PLX3397-treated mice compared to controls.

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Funding

Competing interests

Declarations. Ethics approval and consent to participate: All experimental procedures, breeding, and housing were conducted in accordance with the guidelines for Animal Care of Osaka University and were approved by the Care and Use of Laboratory Animals Committee of Osaka University Graduate School of Medicine. Consent for publication: All authors have read and approved the final manuscript. Competing interests: The authors declare no competing interests.

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Interactions between brain immune cells and T cells may promote harmful protein buildup in a Parkinson's disease mouse model

Abstract

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