Imbalance between T helper 1 and regulatory T cells plays a detrimental role in experimental Parkinson’s disease in mice

Li, Wenjie; Luo, Yuan; Xu, Hongyu; Ma, Qianqian; Yao, Qi

doi:10.1177/0300060521998471

Cited by 22 publications

(17 citation statements)

References 32 publications

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“…Concerning animal studies, Reynolds et al demonstrated a neuroprotective role for Tregs in the MPTP mouse model of PD: the adoptive transfer of CD3-activated Tregs to MPTP-intoxicated mice protected the nigrostriatal system in a dose-dependent manner [ 42 ], probably by attenuating Th17-mediated neurodegeneration [ 5 ]. Also in the MPTP mouse model examined by Li et al, Treg transfer along with anti-TNF α antibody administration increased Tregs and reduced Th1 cells leading to an amelioration of PD severity [ 43 ].…”

Section: Changes Of Peripheral Cd4 + and Cd8 + T Cells In Pd Patientsmentioning

confidence: 99%

T Lymphocytes in Parkinson’s Disease

Contaldi

Magistrelli

Comi

2022

JPD

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T cells are key mediators of both humoral and cellular adaptive immune responses, and their role in Parkinson’s disease (PD) is being increasingly recognized. Several lines of evidence have highlighted how T cells are involved in both the central nervous system and the periphery, leading to a profound imbalance in the immune network in PD patients. This review discusses the involvement of T cells in both preclinical and clinical studies, their importance as feasible biomarkers of motor and non-motor progression of the disease, and recent therapeutic strategies addressing the modulation of T cell response.

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Section: Changes Of Peripheral Cd4 + and Cd8 + T Cells In Pd Patientsmentioning

confidence: 99%

T Lymphocytes in Parkinson’s Disease

Contaldi

Magistrelli

Comi

2022

JPD

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“…In spite of discrepancies relating to T cell subset numbers, a change in the ability of Treg cells to function properly would result in homeostatic deviations regardless of cell numbers. More research is needed to clarify the uncertainties in the field, but most of the literature available suggests that the inflammation observed during PD is partly due to a T cell subset imbalance, which favors inflammation [ 52 , 196 ]. Better understanding of the mechanisms behind PD and how the immune system is involved will hopefully lend to the development of effective therapies for PD.…”

Section: Adaptive Immunity and Parkinson’s Diseasementioning

confidence: 99%

The role of the adaptive immune system and T cell dysfunction in neurodegenerative diseases

DeMaio

Mehrotra

Sambamurti

et al. 2022

J Neuroinflammation

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The adaptive immune system and associated inflammation are vital in surveillance and host protection against internal and external threats, but can secondarily damage host tissues. The central nervous system is immune-privileged and largely protected from the circulating inflammatory pathways. However, T cell involvement and the disruption of the blood–brain barriers have been linked to several neurodegenerative diseases including Parkinson's disease, Alzheimer’s disease, and multiple sclerosis. Under normal physiological conditions, regulatory T cells (Treg cells) dampen the inflammatory response of effector T cells. In the pathological states of many neurodegenerative disorders, the ability of Treg cells to mitigate inflammation is reduced, and a pro-inflammatory environment persists. This perspective review provides current knowledge on the roles of T cell subsets (e.g., effector T cells, Treg cells) in neurodegenerative and ocular diseases, including uveitis, diabetic retinopathy, age-related macular degeneration, and glaucoma. Many neurodegenerative and ocular diseases have been linked to immune dysregulation, but the cellular events and molecular mechanisms involved in such processes remain largely unknown. Moreover, the role of T cells in ocular pathologies remains poorly defined and limited literature is available in this area of research. Adoptive transfer of Treg cells appears to be a vital immunological approach to control ocular pathologies. Similarities in T cell dysfunction seen among non-ocular neurodegenerative diseases suggest that this area of research has a great potential to develop better therapeutic agents for ocular diseases and warrants further studies. Overall, this perspective review article provides significant information on the roles of T cells in numerous ocular and non-ocular neurodegenerative diseases.

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“…Treg cell administration results in reduction of pro-inflammatory cytokines (IL-17, IL-22, IFN- γ , TNF- α , and IL-1 β ) in the SN of MPTP-treated mice. Studies demonstrate anti-TNF- α neutralizing antibodies in combination with Treg cell administration significantly reduce Th1 cell populations [ 6 , 82 ]. Additionally, polyclonal Treg cells activated by anti-CD3 antibodies upregulate anti-inflammatory cytokines, IL-10 and transforming growth factor- β (TGF- β ), in the ventral midbrains of MPTP-treated mice, significantly attenuating neuroinflammation and inhibiting microglial activation [ 80 ].…”

Section: Anti-inflammatory T-cells Neuroprotective Role In Pdmentioning

confidence: 99%

Calpain activation and progression of inflammatory cycles in Parkinson’s disease

Gao¹,

McCoy²,

Zaman³

et al. 2022

Front. Biosci. (Landmark Ed)

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Parkinson's disease (PD) is a progressive, neurodegenerative condition of the central nervous system (CNS) affecting 6.3 million people worldwide with no curative treatments. Current therapies aim to mitigate PD's effects and offer symptomatic relief for patients. Multiple pathways are involved in the pathogenesis of PD, leading to neuroinflammation and the destruction of dopaminergic neurons in the CNS. This review focuses on PD pathology and the role of calpain, a neutral protease, as a regulator of various immune cells such as T-cells, microglia and astrocytes which lead to persistent neuroinflammatory responses and neuronal loss in both the brain and spinal cord (SC). Calpain plays a significant role in the cleavage and aggregation of toxic α-synuclein (α-syn), a presynaptic neural protein, and other organelles, contributing to mitochondrial dysfunction and oxidative stress. α-Syn aggregation results in the formation of Lewy bodies (LB) that further contribute to neuronal damage through lipid bilayer penetration, calcium ion (Ca 2+ ) influx, oxidative stress and damage to the blood brain barrier (BBB). Dysfunctional mitochondria destabilize cytosolic Ca 2+ concentrations, raising intracellular Ca 2+ ; this leads to excessive calpain activation and persistent inflammatory responses. α-Syn aggregation also results in the disruption of dopamine synthesis through phosphorylation of tyrosine hydroxylase (TH), a key enzyme involved in the conversion of tyrosine to levodopa (L-DOPA), the amino acid precursor to dopamine. Decreased dopamine levels result in altered dopamine receptor (DR) signaling, ultimately activating pro-inflammatory T-cells to further contribute to the inflammatory response. All of these processes, together, result in neuroinflammation, degeneration and ultimately neuronal death seen in PD. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP-a prodrug to the neurotoxin 1-methyl-4-phenylpyridinium (MPP+)), rotenone (an environmental neurotoxin), and 6-hydroxydopamine (6-OHDA -a neurotoxic synthetic organic compound) induce PD-like conditions when injected into rodents. All three agents work through similar mechanisms and lead to degeneration of dopaminergic neurons in the substantia nigra (SN) and more recently discovered in motor neurons of the spinal cord (SC). These neurotoxins also increase calpain activity, furthering the neuroinflammatory response. Hence, calpain inhibitors have been posited as potential therapeutics for PD to prevent calpain-related inflammation and neurodegenerative responses in not only the SN but the SC as well.

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Imbalance between T helper 1 and regulatory T cells plays a detrimental role in experimental Parkinson’s disease in mice

Cited by 22 publications

References 32 publications

T Lymphocytes in Parkinson’s Disease

T Lymphocytes in Parkinson’s Disease

The role of the adaptive immune system and T cell dysfunction in neurodegenerative diseases

Calpain activation and progression of inflammatory cycles in Parkinson’s disease

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