Cells, Molecules and Mechanisms Involved in the Neuro-Immune Interaction

Pacheco, Rodrigo; Contreras, Francisco; Prado, Carolina

doi:10.5772/48367

Cited by 17 publications

(26 citation statements)

References 47 publications

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“…2). Importantly, there is substantial evidence showing that neurotransmitters may alter the function not only of neurons but also of microglia and several populations of immune cells, including CD4+ T-cells, dendritic cells and macrophages (Pacheco et al 2012). In this section w e p r o v i d e e v i d e n c e l i n k i n g t h e i m b a l a n c e i n neurotransmitter/neuromodulator levels with increased neuroinflammation in PD, with a special focus on the regulation of CD4+ T-cell function.…”

Section: Neurotransmitters As Modulators Of Encephalitogenic T-cells mentioning

confidence: 99%

Regulation of the Neurodegenerative Process Associated to Parkinson’s Disease by CD4+ T-cells

González

Contreras

Pacheco

2015

J Neuroimmune Pharmacol

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Neuroinflammation constitutes a fundamental process involved in the physiopathology of Parkinson's disease (PD). Microglial cells play a central role in the outcome of neuroinflammation and consequent neurodegeneration of dopaminergic neurons in the substantia nigra. Current evidence indicates that CD4+ T-cells infiltrate the central nervous system (CNS) in PD, where they play a critical role determining the functional phenotype of microglia, thus regulating the progression of the neurodegenerative process. Here, we first analysed the pathogenic role of inflammatory phenotypes and the beneficial role of anti-inflammatory phenotypes of encephalitogenic CD4+ T-cells involved in the physiopathology of PD. Next, we discussed how alterations of neurotransmitter levels observed in the basal ganglia throughout the time course of PD progression could be strongly affecting the behaviour of encephalitogenic CD4+ T-cells and thereby the outcome of the neuroinflammatory process and the consequent neurodegeneration of dopaminergic neurons. Afterward, we integrated the evidence indicating the involvement of an antigen-specific immune response mediated by T-cells and B-cells against CNS-derived self-constituents in PD. Consistent with the involvement of a relevant autoimmune component in PD, we also reviewed the polymorphisms of both, class I and class II major histocompatibility complexes, associated to the risk of PD. Overall, this study gives an overview of how an autoimmune component involved in PD plays a fundamental role in the progression of the neurodegenerative process.

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Section: Neurotransmitters As Modulators Of Encephalitogenic T-cells mentioning

confidence: 99%

Regulation of the Neurodegenerative Process Associated to Parkinson’s Disease by CD4+ T-cells

González

Contreras

Pacheco

2015

J Neuroimmune Pharmacol

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“…The resulting CD4 T cell-derived acetylcholine activates nAChR expressed by splenic macrophages, suppressing the production of TNF-α and other proinflammatory cytokines (52,54). Thus, in addition to local modulation of inflammation, neuron-lymphocyte interactions can also play a role in complex neuroimmunomodulatory circuits (4). Finally, the impact of lymphocytes on CNS neurons, neurophysiology, and behavior is an area of extensive research in the neuroimmunology field (197).…”

Section: Neuron-t Cell Interactionsmentioning

confidence: 99%

“…Neuro-immune interactions are mostly mediated by soluble factors such as neurotransmitters, neuropeptides, and cytokines (2). Immune cells are equipped to respond to neuronal signals by expressing receptors for neuronal cell-derived molecules and, reciprocally, neurons express receptors for immune-derived cytokines and neurotransmitters, which can affect neuronal function (3)(4)(5). As such, neuro-immune interactions have been involved in multiple aspects of tissue physiology and have also been described in several conditions, including autism, cancer, multiple sclerosis, and chronic inflammatory disorders (2).…”

Section: Introductionmentioning

confidence: 99%

Neuro–Immune Cell Units: A New Paradigm in Physiology

Godinho-Silva

Cardoso²,

Veiga-Fernandes³

2019

Annu. Rev. Immunol.

169

150

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The interplay between the immune and nervous systems has been acknowledged in the past, but only more recent studies have started to unravel the cellular and molecular players of such interactions. Mounting evidence indicates that environmental signals are sensed by discrete neuro–immune cell units (NICUs), which represent defined anatomical locations in which immune and neuronal cells colocalize and functionally interact to steer tissue physiology and protection. These units have now been described in multiple tissues throughout the body, including lymphoid organs, adipose tissue, and mucosal barriers. As such, NICUs are emerging as important orchestrators of multiple physiological processes, including hematopoiesis, organogenesis, inflammation, tissue repair, and thermogenesis. In this review we focus on the impact of NICUs in tissue physiology and how this fast-evolving field is driving a paradigm shift in our understanding of immunoregulation and organismal physiology.

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“…During the past two decades, several studies have shown the capability of several neurotransmitters to regulate the function and differentiation of immune cells, including acetyl-choline, serotonin, glutamate, and dopamine (DA) among others (11)(12)(13)(14)(15)(16)(17)(18). Regarding expression of DA receptors (DARs) in immune cells, these receptors have been found not only in cells of the innate immune response such as dendritic cells (DCs), NK cells, macrophages/monocytes and granulocytes (19)(20)(21) but also in cells of the adaptive immune response such as B cells, CD8 + T cells, and CD4 + T cells (22)(23)(24)(25)(26)(27)(28)(29)(30).…”

Section: P Arkinson's Disease (Pd) Is a Neurodegenerative Disordermentioning

confidence: 99%

Dopamine Receptor D3 Expressed on CD4+ T Cells Favors Neurodegeneration of Dopaminergic Neurons during Parkinson’s Disease

González

Contreras

Prado

et al. 2013

The Journal of Immunology

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128

145

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Emerging evidence has demonstrated that CD4+ T cells infiltrate into the substantia nigra (SN) in Parkinson's disease (PD) patients and in animal models of PD. SN-infiltrated CD4+ T cells bearing inflammatory phenotypes promote microglial activation and strongly contribute to neurodegeneration of dopaminergic neurons. Importantly, altered expression of dopamine receptor D3 (D3R) in PBLs from PD patients has been correlated with disease severity. Moreover, pharmacological evidence has suggested that D3R is involved in IFN-γ production by human CD4+ T cells. In this study, we examined the role of D3R expressed on CD4+ T cells in neurodegeneration of dopaminergic neurons in the SN using a mouse model of PD. Our results show that D3R-deficient mice are strongly protected against loss of dopaminergic neurons and microglial activation during 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. Notably, D3R-deficient mice become susceptible to MPTP-induced neurodegeneration and microglial activation upon transfer of wild-type (WT) CD4+ T cells. Furthermore, RAG1 knockout mice, which are devoid of T cells and are resistant to MPTP-induced neurodegeneration, become susceptible to MPTP-induced loss of dopaminergic neurons when reconstituted with WT CD4+ T cells but not when transferred with D3R-deficient CD4+ T cells. In agreement, experiments analyzing activation and differentiation of CD4+ T cells revealed that D3R favors both T cell activation and acquisition of the Th1 inflammatory phenotype. These findings indicate that D3R expressed on CD4+ T cells plays a fundamental role in the physiopathology of MPTP-induced PD in a mouse model.

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Cells, Molecules and Mechanisms Involved in the Neuro-Immune Interaction

Cited by 17 publications

References 47 publications

Regulation of the Neurodegenerative Process Associated to Parkinson’s Disease by CD4+ T-cells

Regulation of the Neurodegenerative Process Associated to Parkinson’s Disease by CD4+ T-cells

Neuro–Immune Cell Units: A New Paradigm in Physiology

Dopamine Receptor D3 Expressed on CD4+ T Cells Favors Neurodegeneration of Dopaminergic Neurons during Parkinson’s Disease

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