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by claude@2026-07, 2026-07-04
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This study used single-cell RNA sequencing together with T-cell receptor sequencing to profile the complete peripheral immune cell compartment in 10 healthy controls and 14 Parkinson’s disease donors, analyzing 78,876 cells to identify immune cell types, subtypes, and T-cell clones. The authors found five major immune cell classes with 38 re-clustered cellular subtypes, including a shift of classical CD14+ monocytes toward an activated CD14+/CD83+ state, altered lymphocyte subtype abundance (including decreased CD4+ naive and mucosal-associated invariant T-cell subtypes and increased CD56+ natural killer cells), and PD-associated T-cell clones shared across multiple patients. They also reported increased expression of activation signature genes, particularly AP-1 stress-response transcription factor complex activity across all PD cell types. A stated limitation is that the paper aims to define signatures rather than provide established diagnostic or progression biomarkers, and it includes disease comparisons showing the activation signal was not present in atypical parkinsonism patients with multiple systems atrophy or progressive supranuclear palsy. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.
Abstract
Parkinson’s Disease (PD) is most recognized for its impact on the central nervous system. However, recent breakthroughs underscore the crucial role of interactions between central and peripheral systems in PD’s pathogenesis. The spotlight is now shifting as we explore beyond the central nervous system, discovering that peripheral changes such as inflammatory dysfunctions may predict the rate of disease progression and severity. Despite more than 200 years of research on PD, reliable diagnostic or progression biomarkers and effective disease-modifying treatments are still lacking. Additionally, the cellular mechanisms that drive changes in immunity are largely unknown. Thus, understanding peripheral immune signatures could lead to earlier diagnosis and more effective treatments for PD. Here, we sought to define the transcriptomic alterations of the complete peripheral immune cell compartment by single-cell RNA- and T-cell receptor-sequencing with hopes of uncovering PD signatures and potential peripheral blood biomarkers. Following transcriptional profiling of 78 876 cells from 10 healthy controls and 14 PD donors, we observed five major classes of immune cell types; myeloid (monocytes, dendritic cells) and lymphoid (T, B, natural killer) cells from which we identified 38 cellular subtypes following bioinformatic re-clustering. Comparing immune cell subtypes and phenotypes between PD patients and healthy controls revealed notable features of PD: 1) a significant shift of classical CD14 + monocytes towards an activated CD14 + /CD83 + state, 2) changes in lymphocyte subtype abundance, including a significant decrease in CD4 + naive and mucosal-associated invariant T-cells subtypes, along with an increase in CD56 + natural killer cells, 3) the identification by T-cell receptor sequencing of several PD specific T-cell clones shared between multiple patients, suggesting the implication of common epitopes in PD pathogenesis, 4) a notable increase in the expression of activation signature genes, including the AP-1 stress-response transcription factor complex, across all PD cell types. This signal was not present in atypical parkinsonism patients with multiple systems atrophy or progressive supranuclear palsy. Overall, we present a comprehensive atlas of peripheral blood mononuclear cells from control and PD patients which should serve as a tool to improve our understanding of the role the immune cell landscape plays in PD pathogenesis.
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Abstract
Parkinson’s Disease (PD) is most recognized for its impact on the central nervous system. However, recent breakthroughs underscore the crucial role of interactions between central and peripheral systems in PD’s pathogenesis. The spotlight is now shifting as we explore beyond the central nervous system, discovering that peripheral changes such as inflammatory dysfunctions may predict the rate of disease progression and severity. Despite more than 200 years of research on PD, reliable diagnostic or progression biomarkers and effective disease-modifying treatments are still lacking. Additionally, the cellular mechanisms that drive changes in immunity are largely unknown. Thus, understanding peripheral immune signatures could lead to earlier diagnosis and more effective treatments for PD. Here, we sought to define the transcriptomic alterations of the complete peripheral immune cell compartment by single-cell RNA- and T-cell receptor-sequencing with hopes of uncovering PD signatures and potential peripheral blood biomarkers.
Following transcriptional profiling of 78 876 cells from 10 healthy controls and 14 PD donors, we observed five major classes of immune cell types; myeloid (monocytes, dendritic cells) and lymphoid (T, B, natural killer) cells from which we identified 38 cellular subtypes following bioinformatic re-clustering. Comparing immune cell subtypes and phenotypes between PD patients and healthy controls revealed notable features of PD: 1) a significant shift of classical CD14+ monocytes towards an activated CD14+/CD83+ state, 2) changes in lymphocyte subtype abundance, including a significant decrease in CD4+ naive and mucosal-associated invariant T-cells subtypes, along with an increase in CD56+ natural killer cells, 3) the identification by T-cell receptor sequencing of several PD specific T-cell clones shared between multiple patients, suggesting the implication of common epitopes in PD pathogenesis, 4) a notable increase in the expression of activation signature genes, including the AP-1 stress-response transcription factor complex, across all PD cell types. This signal was not present in atypical parkinsonism patients with multiple systems atrophy or progressive supranuclear palsy.
Overall, we present a comprehensive atlas of peripheral blood mononuclear cells from control and PD patients which should serve as a tool to improve our understanding of the role the immune cell landscape plays in PD pathogenesis.
Competing Interest Statement
The authors have declared no competing interest.
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