CCL5–Glutamate Cross-Talk in Astrocyte-Neuron Communication in Multiple Sclerosis

Pittaluga, Anna

doi:10.3389/fimmu.2017.01079

Cited by 57 publications

(43 citation statements)

References 159 publications

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“…These findings, in addition to our data, suggest that CCL5 may be a target for therapeutic intervention in human rabies. However, CCL5 plays a role in controlling neurotransmission by modulating glutamate release at the synapses [89,90] and dysregulation of CCL5 mediated glutamatergic transmission is linked with psychiatric disorders [89][90][91][92]. In addition, CCL5 also promotes neuronal survival during injury involving toxic insults [93,94].…”

Section: Discussionmentioning

confidence: 99%

Modelling Lyssavirus Infections in Human Stem Cell-Derived Neural Cultures

Sundaramoorthy

Gödde

Farr

et al. 2020

Viruses

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Rabies is a zoonotic neurological infection caused by lyssavirus that continues to result in devastating loss of human life. Many aspects of rabies pathogenesis in human neurons are not well understood. Lack of appropriate ex-vivo models for studying rabies infection in human neurons has contributed to this knowledge gap. In this study, we utilize advances in stem cell technology to characterize rabies infection in human stem cell-derived neurons. We show key cellular features of rabies infection in our human neural cultures, including upregulation of inflammatory chemokines, lack of neuronal apoptosis, and axonal transmission of viruses in neuronal networks. In addition, we highlight specific differences in cellular pathogenesis between laboratory-adapted and field strain lyssavirus. This study therefore defines the first stem cell-derived ex-vivo model system to study rabies pathogenesis in human neurons. This new model system demonstrates the potential for enabling an increased understanding of molecular mechanisms in human rabies, which could lead to improved control methods.

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Section: Discussionmentioning

confidence: 99%

Modelling Lyssavirus Infections in Human Stem Cell-Derived Neural Cultures

Sundaramoorthy

Gödde

Farr

et al. 2020

Viruses

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“…The concept of bidirectional neuron–glia communication via CKs and other cytokines, one the one hand, and neurotransmitters and neuropeptides, on the other, is central to understanding physiological functionalities and pathological distortions. Certain inflammatory CKs cause synaptic hyperexcitability by altering glutamatergic and GABAergic neurotransmission and affect neuroplasticity ( 65 ).…”

Section: Cks/cytokines and Their Receptorsmentioning

confidence: 99%

Advances in Biomarker-Guided Therapy for Pediatric- and Adult-Onset Neuroinflammatory Disorders: Targeting Chemokines/Cytokines

Pranzatelli

2018

Front. Immunol.

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The concept and recognized components of “neuroinflammation” are expanding at the intersection of neurobiology and immunobiology. Chemokines (CKs), no longer merely necessary for immune cell trafficking and positioning, have multiple physiologic, developmental, and modulatory functionalities in the central nervous system (CNS) through neuron–glia interactions and other mechanisms affecting neurotransmission. They issue the “help me” cry of neurons and astrocytes in response to CNS injury, engaging invading lymphoid cells (T cells and B cells) and myeloid cells (dendritic cells, monocytes, and neutrophils) (adaptive immunity), as well as microglia and macrophages (innate immunity), in a cascade of events, some beneficial (reparative), others destructive (excitotoxic). Human cerebrospinal fluid (CSF) studies have been instrumental in revealing soluble immunobiomarkers involved in immune dysregulation, their dichotomous effects, and the cells—often subtype specific—that produce them. CKs/cytokines continue to be attractive targets for the pharmaceutical industry with varying therapeutic success. This review summarizes the developing armamentarium, complexities of not compromising surveillance/physiologic functions, and insights on applicable strategies for neuroinflammatory disorders. The main approach has been using a designer monoclonal antibody to bind directly to the chemo/cytokine. Another approach is soluble receptors to bind the chemo/cytokine molecule (receptor ligand). Recombinant fusion proteins combine a key component of the receptor with IgG1. An additional approach is small molecule antagonists (protein therapeutics, binding proteins, and protein antagonists). CK neutralizing molecules (“neutraligands”) that are not receptor antagonists, high-affinity neuroligands (“decoy molecules”), as well as neutralizing “nanobodies” (single-domain camelid antibody fragment) are being developed. Simultaneous, more precise targeting of more than one cytokine is possible using bispecific agents (fusion antibodies). It is also possible to inhibit part of a signaling cascade to spare protective cytokine effects. “Fusokines” (fusion of two cytokines or a cytokine and CK) allow greater synergistic bioactivity than individual cytokines. Another promising approach is experimental targeting of the NLRP3 inflammasome, amply expressed in the CNS and a key contributor to neuroinflammation. Serendipitous discovery is not to be discounted. Filling in knowledge gaps between pediatric- and adult-onset neuroinflammation by systematic collection of CSF data on CKs/cytokines in temporal and clinical contexts and incorporating immunobiomarkers in clinical trials is a challenge hereby set forth for clinicians and researchers.

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“…[8] There is clear evidence that CCL5 and CCR5 are strongly related to many immune-mediated diseases, such as rheumatoid arthritis (RA), multiple sclerosis (MS) and graft-versus-host disease (GVHD). [9][10][11][12][13] Although previous studies have reported that CCL5 and CCR5 are upregulated in OLP, the biological effects of the CCL5-CCR5 axis on OLP T cells remains poorly understood. [14,15] In this study, we detected the expression level of the CCL5-CCR5 axis both in the peripheral blood and local OLP lesions.…”

mentioning

confidence: 99%

Expression and biological functions of the CCL5‐CCR5 axis in oral lichen planus

Shan

Wang

et al. 2019

Experimental Dermatology

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Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disorder with T cell‐mediated immunological pathogenesis. C‐C motif chemokine ligand 5 (CCL5) and its receptor C‐C motif chemokine receptor 5 (CCR5) play important roles in the activation and recruitment of T cells. This study sought to explore the expression and biological functions of the CCL5‐CCR5 axis in OLP. We examined the expression of the CCL5‐CCR5 axis in the peripheral blood and oral tissue of healthy controls and patients with OLP using quantitative real‐time PCR, Simple Western assays, enzyme‐linked immunosorbent assay (ELISA) and immunohistochemistry. In addition, we investigated the effects of the CCL5‐CCR5 axis on the proliferation, apoptosis and migration of OLP T cells using Cell Counting Kit‐8 (CCK8) assay, flow cytometry and transwell assay. We found that the expression of the CCL5‐CCR5 axis was significantly elevated both in the peripheral blood and oral tissue of patients with OLP compared with healthy controls. CCL5 not only promoted OLP T‐cell proliferation and migration but also inhibited OLP T‐cell apoptosis. Moreover, CCR5 inhibition suppressed OLP T‐cell proliferation and migration, whereas OLP T‐cell apoptosis was promoted. In conclusion, our data suggest that the CCL5‐CCR5 axis may be closely related to the inflammatory infiltration of T cells in OLP.

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CCL5–Glutamate Cross-Talk in Astrocyte-Neuron Communication in Multiple Sclerosis

Cited by 57 publications

References 159 publications

Modelling Lyssavirus Infections in Human Stem Cell-Derived Neural Cultures

Modelling Lyssavirus Infections in Human Stem Cell-Derived Neural Cultures

Advances in Biomarker-Guided Therapy for Pediatric- and Adult-Onset Neuroinflammatory Disorders: Targeting Chemokines/Cytokines

Expression and biological functions of the CCL5‐CCR5 axis in oral lichen planus

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