The PD-specific gene signature in T cells appears to be responsible for targeting alpha-synuclein and potentially causing ongoing inflammation in cases of PD, researchers report in the journal npj Parkinson's Disease.
"Parkinson's disease is not usually seen as an autoimmune disease. But all of our work points toward T cells having a role in the disease," co-lead investigator Dr. Cecilia Lindestam Arlehamn of La Jolla Institute for Immunology (LJI), in California, says in a news release.
"Now that we can see what these T cells are doing, we think intervening with antibody therapies could have an impact on the disease progression, especially early on," adds LJI professor Dr. Alessandro Sette, who also worked on the study.
While the etiology of PD is largely unknown, recent evidence suggests PD-associated autoimmune features including roles for T cells.
To further characterize the role of T cells, the researchers performed RNA sequencing of peripheral blood mononuclear cells and peripheral CD4 and CD8 memory T cell subsets derived from 34 PD patients and 19 age-matched healthy controls.
"When the groups were stratified by their T cell responsiveness to alpha-synuclein as a proxy for ongoing inflammatory autoimmune response, the study revealed a broad differential gene expression profile in memory T cell subsets and a specific PD-associated gene signature," the researchers report in their article.
"We identified a significant enrichment of transcriptomic signatures previously associated with PD, including for oxidative stress, phosphorylation, autophagy of mitochondria, cholesterol metabolism and inflammation, and the chemokine signaling proteins CX3CR1, CCR5 and CCR1," they add.
"In addition, we identified genes in these peripheral cells that have previously been shown to be involved in PD pathogenesis and expressed in neurons, such as LRRK2, LAMP3, and aquaporin," they say.
"Together, these findings suggest that features of circulating T cells with alpha-synuclein-specific responses in PD patients provide insights into the interactive processes that occur during PD pathogenesis and suggest potential intervention targets," the study team concludes.
Going forward, they plan to study post-mortem brain samples to confirm whether the same self-reactive T cells found in blood also target neurons in people with PD. They will also look for antigens that might be recognized by T cells in individuals with PD.
It will also be important to determine if it's possible to activate or inhibit different genes at different stages of Parkinson's progression, they say.
"We have many avenues now for future research," Dr. Sette says in a news release.
This research was supported by The Michael J. Fox Foundation for Parkinson's Research, the Aligning Science Across Parkinson's (ASAP) initiative, the National Institutes of Health and the JPB Foundation. The authors have no relevant disclosures.
SOURCE: https://go.nature.com/3Iwsx9A npj Parkinson's Disease, online March 21, 2022.
By Reuters Staff
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