What role does the immune response in the initiation and progression of Parkinson’s disease?
Parkinson’s disease (PD) is a prevalent neurodegenerative disorder characterized by a progressive decline in motor function. In addition to loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and deposition of Lewy bodies composed of aggregated phosphorylated α-synuclein (a-syn) in the surviving neurons, the brain sustains chronic inflammation marked by infiltration of CD4+ and CD8+ T lymphocytes and persistent microglial activation.
The inflammation associated with PD is not limited to the brain, as patients experience chronic, elevated inflammation in the gut and increased serum levels of proinflammatory cytokines. However, whether brain inflammation and T lymphocyte infiltration into the affected regions are drivers or consequences of PD pathology remains unclear.
Ongoing work in the Agalliu lab has been investigating the role of the adaptive immune system in PD in human patients, a new mouse model, and primary cultures.
- Garretti F, Monahan C, Sloan N, Bergen J, Shahriar S, Kim SW, Sette A, Cutforth T, Kanter E, Agalliu D, Sulzer D. Interaction of an α-synuclein epitope with HLA-DRB1∗15:01 triggers enteric features in mice reminiscent of prodromal Parkinson's disease. Neuron. 2023 Aug 11:S0896-6273(23)00548-2. doi: 10.1016/j.neuron.2023.07.015. Epub ahead of print. PMID: 37597517.
- Garretti F, Monahan C, Sette A, Agalliu D, Sulzer D. T cells, α-synuclein and Parkinson disease. Handb Clin Neurol. 2022;184:439-455. doi: 10.1016/B978-0-12-819410-2.00023-0.
- Garretti F, Agalliu D, Lindestam Arlehamn CS, Sette A, Sulzer D. (2019) Autoimmunity in Parkinson’s Disease: The Role of α-Synuclein-Specific T Cells. Front Immunol Feb 25;10:303.
Role of T cells in Parkinson’s disease pathophysiology.
In the Agalliu lab, Connor has been utilizing a novel mouse model of Parkinson’s disease to investigate the mechanisms the adaptive immune response to alpha synuclein and development of prodromal PD.