IL-21 and IL-21 Receptor Expression in Lymphocytes and Neurons in Multiple Sclerosis Brain

Tzartos, John; Craner, Matthew; Friese, Manuel A.; Jakobsen, Karen B.; Newcombe, Jia; Esiri, Margaret M.; Fugger, Lars

doi:10.1016/j.ajpath.2010.10.043

Cited by 120 publications

(96 citation statements)

References 47 publications

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“…Supporting this idea, it has been demonstrated in vitro that several cytokines, including IFN-α [135], IL-10 [136] and IL-21 [137], induce LMP-1 expression in EBV infected B-cells. Notably, it has been shown that the expression of these cytokines are increased in diseased organs of patients with MS [107,138,139] and RA [140,141,142,143] and in the blood of patients with SLE [130,144,145]. Moreover, cross-linking of the B-cell receptor of EBV infected B-cells activates transcription of BZLF-1, resulting in lytic EBV replication [146].…”

Section: Viral Mechanismsmentioning

confidence: 99%

Epstein-Barr Virus in Systemic Lupus Erythematosus, Rheumatoid Arthritis and Multiple Sclerosis—Association and Causation

Lossius

Johansen

Torkildsen

et al. 2012

Viruses

116

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Epidemiological data suggest that the Epstein-Barr virus (EBV) is associated with several autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis. However, it is not clear whether EBV plays a role in the pathogenesis of these diseases, and if so, by which mechanisms the virus may contribute. In this review, we discuss possible viral and immunological mechanisms that might explain associations between EBV and autoimmune diseases and whether these associations represent causes or effects of inflammation and autoimmunity.

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Section: Viral Mechanismsmentioning

confidence: 99%

Epstein-Barr Virus in Systemic Lupus Erythematosus, Rheumatoid Arthritis and Multiple Sclerosis—Association and Causation

Lossius

Johansen

Torkildsen

et al. 2012

Viruses

116

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“…A mechanism underlying Th17-mediated neurotoxicity in neurodegenerative diseases such as multiple sclerosis is the binding of proinflammatory cytokines released by Th17 cells to their relevant receptors on neurons, which induces neuronal apoptosis or death [15]. In addition, a direct contact between Th17 cells and neurons in Parkinson's disease (PD) that results in neuronal apoptosis or death is also presented [16].…”

Section: Introductionmentioning

confidence: 99%

Th17 Cell-Mediated Neuroinflammation Is Involved in Neurodegeneration of Aβ1-42-Induced Alzheimer’s Disease Model Rats

et al. 2013

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Neuroinflammation, especially innate immunocyte-mediated neuroinflammation, has been reported to participate in pathogenesis of Alzheimer’s disease (AD). However, the involvement of adaptive immune cells, such as CD4+ T lymphocytes, in pathogenesis of AD is not well clarified. Herein, we focus on T helper 17 (Th17) cells, a subpopulation of CD4+ T cells with high proinflammation, and show the implication of the cells in neurodegeneration of AD. Amyloid β1-42 (Aβ1-42) was bilaterally injected into hippocampus of rats to induce AD. On days 7 and 14 following the Aβ1-42 administration, escape latency of the rats in Morris water maze was increased, expression of amyloid precursor protein was upregulated, but expression of protein phosphatase 2A was downregulated in the hippocampus, and Nissl stain showed neuronal loss and gliosis in CA1 region. Infusion of FITC-linked albumin in blood circulation and combination with immunostaining of hippocampal sections for RORγ, a specific transcriptional factor of Th17 cells, demonstrated blood-brain barrier (BBB) disruption and Th17 cells’ infiltration into brain parenchyma of AD rats. Expression of Th17 proinflammatory cytokines, interleukin (IL)-17 and IL-22, was increased in the hippocampus, and concentrations of the two cytokines were elevated in both the cerebrospinal fluid and the serum in AD occurrence and development. Compared with intact or saline-treated control rats, AD animals indicated an upregulated expression of Fas and FasL in the hippocampus. Further, the immunofluorescent histochemistry on AD hippocampal sections with NeuN, RORγ, Fas and FasL displayed that Fas was principally expressed by neurons and FasL was predominantly expressed by Th17 cells, and that neuronal apoptosis shown by TUNEL and NeuN double-labeled cells increased. These results suggest that Th17 cells, which were infiltrated into AD brain parenchyma, participate in neuroinflammation and neurodegeneration of AD by release of proinflammatory cytokines and by direct action on neurons via Fas/FasL apoptotic pathway.

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“…In this study, John and coworkers investigated Il-21/Il-21R expression in MS lesions by in situ hybridization and immunohistochemistry. They detected strongly Il-21 + infiltrating cells predominantly in acute but also in chronic active white matter MS lesions 38 . Therefore, additional studies using much larger sample sizes and more advanced technology will be required to ascertain contributions of Il-21 to MS pathogenesis.…”

Section: Figure 6: Il-21 Level Was Much Higher In the Autoantibody-pomentioning

confidence: 99%

Cerebrospinal Fluid IL-21 Levels in Neuromyelitis Optica and Multiple Sclerosis

Zhong²,

Wang³

et al. 2012

Can. J. Neurol. Sci.

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Neuromyelitis optica (NMO) and Multiple sclerosis (MS) are two typical inflammatory demyelinating diseases of the central nervous system (CNS) with complex pathogenesis, and they share many similarities. Neuromyelitis optica was considered an optic-spinal form of MS until specific antibodies (NMO-IgG) were suggested to be a biomarker of NMO, distinguishing it from conventional MS 1 . T cells have emerged as a key player in the pathogenesis of MS 2 . We also found increased levels of CD4 + T cells in NMO patients 3 . Simultaneously, B cells are believed to play an important role in the pathogenesis of these diseases. A role of B cells in MS pathogenesis has been suggested by the presence of oligoclonal immunoglobulin bands (OCBs) in cerebrospinal fluid (CSF) 4,5 . In addition, NMO-IgG is compelling evidence for B cells involvement in NMO pathogenesis 6 . Moreover, therapies which eliminate antibodies ABSTRACT: Background: Neuromyelitis optica (NMO) and multiple sclerosis (MS) are inflammatory demyelinating diseases of human central nervous system (CNS) with complex pathogenesis. Il-21/Il-21R regulates activation, proliferation and survival of both T cells and B cells, which are involved in the pathogenesis of NMO and MS. High levels of serum Il-21 were observed in NMO patients. However, concentration of cerebrospinal fluid (CSF) Il-21 in MS and NMO patients still remain unknown. Object: To detect the CSF concentration of Il-21 in NMO and MS patients and to evaluate its relationship with disease activity, particularly concerned about its impact on humoral immunity. Methods: CSF Il-21 was detected by an enzyme-linked immunosorbent assay (elISA) in NMO patients (n=21), MS patients (n=20) and controls (n=16). Results: CSF concentration of the Il-21 was noticeably elevated in NMO (p=0.012) and borderline significantly increased in MS (p=0.115). In addition, this occurrence was associated with humoral immune activity as shown by a correlation between Il-21 and complement in NMO cohort (p=0.023) and high Il-21 levels in autoantibodypositive subgroup (p=0.027). Conclusions: The concentration of CSF Il-21 was noticeably elevated and might have a positive correlation with humoral immune activity in NMO. RÉSUMÉ: Les niveaux d'IL-21 du liquide céphalo-rachidien dans

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IL-21 and IL-21 Receptor Expression in Lymphocytes and Neurons in Multiple Sclerosis Brain

Cited by 120 publications

References 47 publications

Epstein-Barr Virus in Systemic Lupus Erythematosus, Rheumatoid Arthritis and Multiple Sclerosis—Association and Causation

Epstein-Barr Virus in Systemic Lupus Erythematosus, Rheumatoid Arthritis and Multiple Sclerosis—Association and Causation

Th17 Cell-Mediated Neuroinflammation Is Involved in Neurodegeneration of Aβ1-42-Induced Alzheimer’s Disease Model Rats

Cerebrospinal Fluid IL-21 Levels in Neuromyelitis Optica and Multiple Sclerosis

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