Parkinson’s disease (PD) is a neurodegenerative disease affecting 7-10 million people worldwide, causing motor and non-motor disturbances. Neuropathological features include progressive loss of substantia nigra pars compacta dopaminergic neurons, intraneuronal inclusions called Lewy bodies, and microglial activation. Microglia sustain neuroinflammation, and peripheral adaptive immunity might be a major determinant in microglial activation leading to neurodegeneration.
Genome-wide association studies identified several genes associated with PD and involved in immunity, as well as common gene variants in the HLA region associated with sporadic PD. Several modifications of peripheral immunity in PD have been reported, including: decreased CD4+/CD8+ T ratios, fewer CD4+CD25+ T cells, increased IFN-gamma/IL-4-producing T cells, decreased CD4+ T cells and CD19+ B cells. CD8+ and CD4+ T cells have been identified in both postmortem human PD brains and in the MPTP mouse model of PD, and evidence from animal models pointed to CD4+ T cells as main determinants of T cell-mediated dopaminergic cell death. Remarkably, increased effector/memory CD4+ T cells and decreased CD31+ and alpha4beta7+ CD4+ T cells have been reported in PD patients, in association with progressive motor dysfunction, suggesting a direct relationship between chronic immune stimulation and disease severity, and specific profiles of serum immune markers, combining pro- and anti-inflammatory cytokines, might be predictive of disease progression, with higher pro-inflammatory and lower anti-inflammatory components being associated with more rapid motor progression and cognitive impairment. As no disease-modifying therapies are currently available for PD, the emerging contribution of peripheral immunity and central neuroinflammation to PD pathogenesis may point to immunomodulation as a novel therapeutic target.
This Research Topic aims to publish high-quality articles covering all the aspects related to the relationship between immunity and neurodegeneration in PD. To this end, we will bring together research teams from different but synergistic scientific fields. The topics we wish to cover include, but are not limited to:
? Peripheral/central immune cross-talk in PD
? Gut-Brain axis contribution to PD pathogenesis
? Immune cells as biomarkers of disease progression
? Immunology of PD animal models and their relevance for human disease
? Potential approaches for peripheral immunomodulation in PD
Contributors are encouraged to submit articles describing novel results, models, viewpoints, perspectives and/or methodological innovations. Contributors are also asked to submit a brief abstract prior to submitting a full-length manuscript, so that the suitability of the proposed article for our Research Topic can be evaluated. We will strive to ensure that the articles of the Topic collectively present a cohesive picture of the state-of-the-art in the field, and help advance our understanding, diagnosis and treatment of PD.
Parkinson’s disease (PD) is a neurodegenerative disease affecting 7-10 million people worldwide, causing motor and non-motor disturbances. Neuropathological features include progressive loss of substantia nigra pars compacta dopaminergic neurons, intraneuronal inclusions called Lewy bodies, and microglial activation. Microglia sustain neuroinflammation, and peripheral adaptive immunity might be a major determinant in microglial activation leading to neurodegeneration.
Genome-wide association studies identified several genes associated with PD and involved in immunity, as well as common gene variants in the HLA region associated with sporadic PD. Several modifications of peripheral immunity in PD have been reported, including: decreased CD4+/CD8+ T ratios, fewer CD4+CD25+ T cells, increased IFN-gamma/IL-4-producing T cells, decreased CD4+ T cells and CD19+ B cells. CD8+ and CD4+ T cells have been identified in both postmortem human PD brains and in the MPTP mouse model of PD, and evidence from animal models pointed to CD4+ T cells as main determinants of T cell-mediated dopaminergic cell death. Remarkably, increased effector/memory CD4+ T cells and decreased CD31+ and alpha4beta7+ CD4+ T cells have been reported in PD patients, in association with progressive motor dysfunction, suggesting a direct relationship between chronic immune stimulation and disease severity, and specific profiles of serum immune markers, combining pro- and anti-inflammatory cytokines, might be predictive of disease progression, with higher pro-inflammatory and lower anti-inflammatory components being associated with more rapid motor progression and cognitive impairment. As no disease-modifying therapies are currently available for PD, the emerging contribution of peripheral immunity and central neuroinflammation to PD pathogenesis may point to immunomodulation as a novel therapeutic target.
This Research Topic aims to publish high-quality articles covering all the aspects related to the relationship between immunity and neurodegeneration in PD. To this end, we will bring together research teams from different but synergistic scientific fields. The topics we wish to cover include, but are not limited to:
? Peripheral/central immune cross-talk in PD
? Gut-Brain axis contribution to PD pathogenesis
? Immune cells as biomarkers of disease progression
? Immunology of PD animal models and their relevance for human disease
? Potential approaches for peripheral immunomodulation in PD
Contributors are encouraged to submit articles describing novel results, models, viewpoints, perspectives and/or methodological innovations. Contributors are also asked to submit a brief abstract prior to submitting a full-length manuscript, so that the suitability of the proposed article for our Research Topic can be evaluated. We will strive to ensure that the articles of the Topic collectively present a cohesive picture of the state-of-the-art in the field, and help advance our understanding, diagnosis and treatment of PD.