Neurotransmitters activate T-cells and elicit crucial functions via neurotransmitter receptors

Levite, Mia

doi:10.1016/j.coph.2008.05.001

Cited by 185 publications

(160 citation statements)

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“…Expression of DARs in T cells, including D3R, is very dynamic and depends on the activation state, specific T cell subset, pathologic conditions, and treatments (15,20,22,26,28,29,(40)(41)(42)(43)(44). In this regard and interestingly, a decreased D3R expression in PBLs obtained from PD patients has been observed, which correlates with the degree of disease severity (34).…”

Section: Discussionmentioning

confidence: 91%

“…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%

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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

127

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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Section: Discussionmentioning

confidence: 91%

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

127

145

View full text Add to dashboard Cite

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“…Receptors for glutamate and GABA are present in lymphocytes, and both neurotransmitters have been shown to exert modulatory effects on the immune response. [103][104][105] Glutamate receptors are differentially expressed in activated versus naïve T-cells, and are believed to contribute to T-cell development and regulation. 106 In addition, glutamate can augment the production of cytokines by lymphocytes, as well as their migratory ability.…”

Section: Neurotransmittersmentioning

confidence: 99%

Immune Dysfunction in Autism: A Pathway to Treatment

2010

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Summary: Autism is a complex and clinically heterogeneous disorder with a spectrum of symptoms. Clinicians, schools, and service agencies worldwide have reported a dramatic increase in the number of children identified with autism. Despite expanding research, the etiology and underlying biological processes of autism remain poorly understood, and the relative contribution from genetic, epigenetic, and environmental factors remains unclear. Although autism affects primarily brain function (especially affect, social functioning, and cognition), it is unknown to what extent other organs and systems are disrupted. Published findings have identified widespread changes in the immune systems of children with autism, at both systemic and cellular levels. Brain specimens from autism subjects exhibit signs of active, ongoing inflammation, as well as alterations in gene pathways associated with immune signaling and immune function. Moreover, many genetic studies have indicated a link between autism and genes that are relevant to both the nervous system and the immune system. Alterations in these pathways can affect function in both systems. Together, these reports suggest that autism may in fact be a systemic disorder with connections to abnormal immune responses. Such immune system dysfunction may represent novel targets for treatment. A better understanding of the involvement of the immune response in autism, and of how early brain development is altered, may have important therapeutic implications.

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“…Since the early evidence that inflammatory signals in the periphery can alter signaling in the hypothalamus [5], the focus has been on identifying a common molecular basis for this bidirectional communication shared through receptors and signaling ligands which cross sequestered anatomical locations [6]. Recent research suggests that neurotransmitters and neurohormones act by binding not only to their classical receptors on target cells in the nervous and endocrine systems, but also to receptors on various immune cells [7], thereby affecting many immunological processes in a powerful and rapid manner [8]. Primary and secondary lymphoid organs are innervated by nervous terminals secreting a variety of neurotransmitters [8].…”

Section: Introductionmentioning

confidence: 99%

“…Recent research suggests that neurotransmitters and neurohormones act by binding not only to their classical receptors on target cells in the nervous and endocrine systems, but also to receptors on various immune cells [7], thereby affecting many immunological processes in a powerful and rapid manner [8]. Primary and secondary lymphoid organs are innervated by nervous terminals secreting a variety of neurotransmitters [8]. Moreover, T-cells (and other immune cells) can also produce and secrete endogenous neuropeptides either spontaneously or after induction by external stimuli [8,9] which then act in an autocrine or paracrine manner to modulate pivotal immune functions, or cross anatomical barriers to facilitate the bidirectional crosstalk with other cells such as neurons or glia [8].…”

Section: Introductionmentioning

confidence: 99%