The role of Th17 cells in auto-inflammatory neurological disorders

Tahmasebinia, Foozhan; Pourgholaminejad, Arash

doi:10.1016/j.pnpbp.2017.07.023

Cited by 85 publications

(74 citation statements)

References 150 publications

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“…GM‐CSF has been connected to exacerbation of multiple sclerosis (MS), Alzheimer's disease, schizophrenia, and Parkinson's disease (Gonzalez & Pacheco, ; Tahmasebinia & Pourgholaminejad, ). Therefore, inhibition of GM‐CSF activity is potentially beneficial, as reported by the use of the monoclonal antibody MOR103 to neutralize GM‐CSF in patients with MS (Constantinescu et al., ) and by blocking the GM‐CSF receptor with antibodies in a mouse model of Charcot‐Marie‐Tooth disease (Klein et al., ).…”

Section: Discussionmentioning

confidence: 99%

Granulocyte‐macrophage colony‐stimulating factor improves mouse peripheral nerve regeneration following sciatic nerve crush

Bombeiro

Pereira

Oliveira

2018

Eur J of Neuroscience

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Peripheral nerve injuries severely impair patients' quality of life as full recovery is seldom achieved. Upon axonal disruption, the distal nerve stump undergoes fragmentation, and myelin breaks down; the subsequent regeneration progression is dependent on cell debris removal. In addition to tissue clearance, macrophages release angiogenic and neurotrophic factors that contribute to axon growth. Based on the importance of macrophages for nerve regeneration, especially during the initial response to injury, we treated mice with granulocyte-macrophage colony-stimulating factor (GM-CSF) at various intervals after sciatic nerve crushing. Sciatic nerves were histologically analyzed at different time intervals after injury for the presence of macrophages and indicators of regeneration. Functional recovery was followed by an automated walking track test. We found that GM-CSF potentiated early axon growth, as indicated by the enhanced expression of growth-associated protein at 7 days postinjury. Inducible nitric oxide synthase expression increased at the beginning and at the end of the regenerative process, suggesting that nitric oxide is involved in axon growth and pruning. As expected, GM-CSF treatment stimulated macrophage infiltration, which increased at 7 and 14 days; however, it did not improve myelin clearance. Instead, GM-CSF stimulated early brain-derived neurotrophic factor (BDNF) production, which peaked at 7 days. Locomotor recovery pattern was not improved by GM-CSF treatment. The present results suggest that GM-CSF may have beneficial effects on early axonal regeneration.

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Section: Discussionmentioning

confidence: 99%

Granulocyte‐macrophage colony‐stimulating factor improves mouse peripheral nerve regeneration following sciatic nerve crush

Bombeiro

Pereira

Oliveira

2018

Eur J of Neuroscience

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“…T lymphocytes are particularly involved in the inflammatory response associated with AD and activated T-cells can easily cross the blood-brain barrier contributing to the ongoing inflammatory repertoire and disease pathogenesis (Togo et al, 2002). In this context, several studies reported the importance of Th17 cells and Th17-derived proinflammatory cytokines such as IL-17, IL-21, IL-22, IL-23, GM-CSF, and IFN-γ in the pathogenesis of AD (Saresella et al, 2011) and in other neurological disorders such as multiple sclerosis and Parkinson's disease (Miossec & Kolls, 2012;Tahmasebinia & Pourgholaminejad, 2017).…”

Section: Introductionmentioning

confidence: 99%

Neutralization of IL‐17 rescues amyloid‐β‐induced neuroinflammation and memory impairment

Cristiano

Volpicelli

Lippiello

et al. 2019

British J Pharmacology

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Background and purpose Alzheimer's disease (AD) is a common neurodegenerative disease characterized by a neuroinflammatory state, and to date, there is no cure and its treatment represents a large unmet clinical need. The involvement of Th17 cells in the pathogenesis of AD‐related neuroinflammation has been reported in several studies. However, the role of the cytokine, IL‐17 has not been well addressed. Herein, we investigate the effects of IL‐17 neutralizing antibody (IL‐17Ab) injected by i.c.v. or intranasal (IN) routes on amyloid‐β (Aβ)‐induced neuroinflammation and memory impairment in mice. Experimental approach Aβ1–42 was injected into cerebral ventricles of adult CD1 mice. These mice received IL‐17Ab via i.c.v. either at 1 h prior to Aβ1–42 injection or IN 5 and 12 days after Aβ1–42 injection. After 7 and 14 days of Aβ1–42 administration, we evaluated olfactory, spatial and working memory and performed biochemical analyses on whole brain and specific brain areas. Key results Pretreatment with IL‐17Ab, given, i.c.v., markedly reduced Aβ1–42‐induced neurodegeneration, improved memory function, and prevented the increase of pro‐inflammatory mediators in a dose‐dependent manner at 7 and 14 days. Similarly, the double IN administration of IL‐17Ab after Aβ1–42 injection reduced neurodegeneration, memory decline, and the levels of proinflammatory mediators and cytokines. Conclusion and implications These findings suggest that the IL‐17Ab reduced neuroinflammation and behavioural symptoms induced by Aβ. The efficacy of IL‐17Ab IN administration in reducing Aβ1–42 neurodegeneration points to a possible future therapeutic approach in patients with AD. Linked Articles This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc

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“…The Th17 cells are increasingly recognized as playing essential roles in driving a number of autoimmune conditions, including SLE, RA, and MS [43,44,45]. In a murine model of retinal autoimmunity, 1,25-(OH) 2 D 3 was shown to inhibit Th17 activity and reduce the expression of IL-17 driven cytokines, namely IL-17 and IL-22/23, in CD4 + memory and CCR6 + T cells [46].…”

Section: Vitamin D Its Nature and Impact On Various Body Systemsmentioning

confidence: 99%

The Impact of Vitamin D on the Immunopathophysiology, Disease Activity, and Extra-Musculoskeletal Manifestations of Systemic Lupus Erythematosus

Mak

2018

IJMS

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Over the past two decades it has been increasingly recognized that vitamin D, aside from its crucial involvement in calcium and phosphate homeostasis and the dynamics of the musculoskeletal system, exerts its influential impact on the immune system. The mechanistic roles that vitamin D plays regarding immune activation for combating infection, as well as pathologically and mediating autoimmune conditions, have been progressively unraveled. In vitro and in vivo models have demonstrated that the action of vitamin D on various immunocytes is not unidirectional. Rather, how vitamin D affects immunocyte functions depends on the context of the immune response, in the way that its suppressive or stimulatory action offers physiologically appropriate and immunologically advantageous outcomes. In this review, the relationship between various aspects of vitamin D, starting from its adequacy in circulation to its immunological functions, as well as its autoimmune conditions, in particular systemic lupus erythematosus (SLE), a prototype autoimmune condition characterized by immune-complex mediated inflammation, will be discussed. Concurring with other groups of investigators, our group found that vitamin D deficiency is highly prevalent in patients with SLE. Furthermore, the circulating vitamin D levels appear to be correlated with a higher disease activity of SLE as well as extra-musculoskeletal complications of SLE such as fatigue, cardiovascular risk, and cognitive impairment.

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The role of Th17 cells in auto-inflammatory neurological disorders

Cited by 85 publications

References 150 publications

Granulocyte‐macrophage colony‐stimulating factor improves mouse peripheral nerve regeneration following sciatic nerve crush

Granulocyte‐macrophage colony‐stimulating factor improves mouse peripheral nerve regeneration following sciatic nerve crush

Neutralization of IL‐17 rescues amyloid‐β‐induced neuroinflammation and memory impairment

The Impact of Vitamin D on the Immunopathophysiology, Disease Activity, and Extra-Musculoskeletal Manifestations of Systemic Lupus Erythematosus

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