Autoimmunity, dendritic cells and relevance for Parkinson’s disease

Koutsilieri, Eleni; Lutz, Manfred B.; Scheller, Carsten

doi:10.1007/s00702-012-0842-7

Cited by 44 publications

(22 citation statements)

References 75 publications

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“…Therefore, the concept that the decrease in circulating DC may be caused by DC enhanced recruitment at the injury site could be extrapolated also to PD neurodegeneration. Indeed, a number of data indirectly suggest that DC, by virtue of their ability to connect the innate and adaptive arms of the immune system, are pivotal in the PD pathogenesis, where an immune response to self antigens may be a causative factor [26], [27]. In addition, it has been previously proposed that blood-derived DC, which can infiltrate the brain during neuroinflammation, may play some role in neurodegeneration [28].…”

Section: Discussionmentioning

confidence: 99%

Blood Dendritic Cell Frequency Declines in Idiopathic Parkinson’s Disease and Is Associated with Motor Symptom Severity

et al. 2013

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The role of inflammation in Parkinson’s Disease (PD) is well appreciated, but its underlying mechanisms are still unclear. Our objective was to determine whether dendritic cells (DC), a unique type of migratory immune cells that regulate immunological response and inflammation have an impact on PD. In a case-control study including 80 PD patients and 80 age- and gender-matched healthy control subjects, the two main blood subsets of plasmacytoid and myeloid DC were defined by flow cytometry analysis. Clinical evaluation of subjects consisting of cognition and depression assessment was performed using the Mini Mental State Examination and the Beck Depression Inventory. The severity of motor symptoms was measured using the Unified Parkinson’s Disease Rating Scale-Part III. Comparison between patient and control DC measures and their relationships with clinical assessments were evaluated.The following main results were obtained: 1) the level of circulating DC (mainly the myeloid subset) was significantly reduced in PD patients in comparison with healthy controls; 2) after controlling for depressive and cognitive characteristics, the frequency of myeloid DC was confirmed as one of the independent determinants of PD; 3) the number of both myeloid and plasmacytoid DC was negatively associated with motor symptom severity. Overall, the decline of blood DC, perhaps due to the recruitment of immune cells to the site of disease-specific lesions, can be considered a clue of the immune alteration that characterizes PD, suggesting innovative exploitations of DC monitoring as a clinically significant tool for PD treatment. Indeed, this study suggests that reduced peripheral blood DC are a pathologically-relevant factor of PD and also displays the urgency to better understand DC role in PD for unraveling the immune system contribution to disease progression and thus favoring the development of innovative therapies ideally based on immunomodulation.

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Section: Discussionmentioning

confidence: 99%

Blood Dendritic Cell Frequency Declines in Idiopathic Parkinson’s Disease and Is Associated with Motor Symptom Severity

et al. 2013

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“…In this regard, the experimental model of PD has shown the infiltration of CD4 + and CD8 + lymphocytes at the sites of neuronal damage (Brochard et al, ; Chandra, Rangasamy, Roy, Kordower, & Pahan, ; Zhou et al, ). In the brain, dendritic cells (DCs) act as antigen‐presenting cells, could migrate to the lymph nodes after activation, and interact with naïve T cells to initiate the T cell–mediated responses (Colton, ; Geissmann et al, ; Koutsilieri, Lutz, & Scheller, ). However, the precise function of DCs in the context of neuroinflammation is still not very well defined.…”

Section: Immune Responses In Pd Pathologymentioning

confidence: 99%

Updates on immunity and inflammation in Parkinson disease pathology

Joshi

Singh

2017

J of Neuroscience Research

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Studies in the last decade have suggested the association of both neuroinflammatory processes and immune responses in Parkinson disease (PD) pathology. PD pathology is related to depleted dopamine levels, α-synuclein aggregation, and death of nigrostriatal dopaminergic neurons. Reports have suggested central and peripheral inflammation in the prodromal stage of the disease, which is sustained during disease progression. Alongside the activation of peripheral immune system exacerbates the dissonant central inflammatory responses and could contribute in synergistic neurodegeneration. Activated glial cells contribute significantly in the neuroinflammatory process during the occurrence of the disease and are also acknowledged as a hallmark of disease progression. However, the contribution of glial cells is not well defined in the context of neurodegeneration and neuroprotection. This review provides an overview of the roles of immune and inflammatory responses and their consequences in PD disease pathogenesis and also discusses possible therapeutic strategies for PD based on these findings.

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“…In addition to multiple sclerosis, neuroinflammation plays a role in the etiology and/or progression also of other CNS diseases. These include Parkinson's disease (Koutsilieri et al 2013), Alzheimer's disease (Fuster-Matanzo et al 2013), bipolar disorder (Stertz et al 2013), and autism (Theoharides et al 2013). In neurodegenerative diseases, one of the mechanisms of progression and damage to healthy neurons in the vicinity of lesions is overactive microglia.…”

Section: Cnsmentioning

confidence: 99%

Insight into the mechanisms of action of estrogen receptor β in the breast, prostate, colon, and CNS

Dey¹,

Barros

Warner

et al. 2013

Journal of Molecular Endocrinology

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Estrogen and its receptors (ERs) influence many biological processes in physiology and pathology in men and women. ERs are involved in the etiology and/or progression of cancers of the prostate, breast, uterus, ovary, colon, lung, stomach, and malignancies of the immune system. In estrogen-sensitive malignancies, ERb usually is a tumor suppressor and ERa is an oncogene. ERb regulates genes in several key pathways including tumor suppression (p53, PTEN); metabolism (PI3K); survival (Akt); proliferation pathways (p45 Skp2 , cMyc, and cyclin E);cell-cycle arresting factors (p21 WAF1

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Autoimmunity, dendritic cells and relevance for Parkinson’s disease

Cited by 44 publications

References 75 publications

Blood Dendritic Cell Frequency Declines in Idiopathic Parkinson’s Disease and Is Associated with Motor Symptom Severity

Blood Dendritic Cell Frequency Declines in Idiopathic Parkinson’s Disease and Is Associated with Motor Symptom Severity

Updates on immunity and inflammation in Parkinson disease pathology

Insight into the mechanisms of action of estrogen receptor β in the breast, prostate, colon, and CNS

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