Interleukin-17 Contributes to Neuroinflammation and Neuropathic Pain Following Peripheral Nerve Injury in Mice

Kim, Cristina Fabiola; Moalem‐Taylor, Gila

doi:10.1016/j.jpain.2010.08.003

Cited by 184 publications

(162 citation statements)

References 70 publications

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“…Activation of Schwann cells in turn promotes their secretion of proinflammatory cytokines, thereby producing a positive feedback mechanism that perpetuates injury 109,110 . Inflammatory cytokines such as IL-1, tumour necrosis factor (TNF) and IL-17 can be produced by many cell types, including Schwann cells, and these factors sensitize Aδ-fibres and C-fibres, triggering neuropathic pain [111][112][113] . Indeed, blocking the TNF signalling pathway with a recombinant human TNF receptorantibody fusion protein has been shown to be beneficial in animal models of diabetic neuro pathy, leading to recovery of nerve conduction velocity and increased expression of myelin basic protein 109 .…”

Section: Box 3 | Satellite Glial Cellsmentioning

confidence: 99%

Schwann cell interactions with axons and microvessels in diabetic neuropathy

et al. 2017

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The incidence of diabetes mellitus has increased dramatically over the past two to three decades. According to the International Diabetes Federation Diabetes Atlas, 415 million people worldwide had diabetes in 2015, and this number is expected to grow by 5% annually, predominantly as a result of increasing prevalence of type 2 diabetes. Furthermore, an estimated 100 million Europeans and 80 million Americans have impaired glucose tolerance or prediabetes. Few people die from acute diabetes in countries with comprehensive health care systems, but the disease is inflicting a huge medical, social and economic burden on society owing to the need for lifelong treatment of its systemic consequences and the insidious development of multi-organ damage.Peripheral neuropathy (BOXES 1,2) is a common but often neglected complication of long-term diabetes, and the lack of treatment options reflects an incomplete understanding of the pathogenic mechanisms. Hyperglycaemia is generally accepted as the primary pathogenic insult in type 1 and type 2 diabetic neuropathy, although roles are emerging for other factors, such as impaired insulin signalling, hypertension and dyslipidaemia (particularly for type 2 diabetes), which might precede overt hyperglycaemia 1 . Many preclinical studies, and occasional clinical studies, have indicated that diabetic neuropathy -like diabetic nephropathy and retinopathy -results from microvascular disease, with a focus on axonal degeneration as a consequence of ischaemia and/or hypoxia. This mechanism, however, is likely to be only one aspect of a more complex pathogenesis.The earliest descriptions of pathology in diabetic neuropathy indicated that Schwannopathy accompanied axonal degeneration. The majority of clinical and basic research in diabetic neuropathy since then has focused on the effects on neurons. However, accumulating data from research into the development and regeneration of the PNS has identified Schwann cells as equally indispensable components that maintain neuronal structure and function, nourish axons, and promote survival and growth upon injury. The early reports from 1979 that demonstrated morphological changes in Schwann cells in human diabetic neuropathy 2 are now supported by an increased awareness of molecular alterations in Schwann cells during diabetes 3 . Schwann cells express a wide range of receptors and, when they sense insults or danger signals, they upregulate synthesis and secretion of factors that stimulate neuroprotection, regrowth and remyelination, or factors that aggravate disease phenotypes 4 . The most recent studies have demonstrated that Schwann cells regulate many aspects of axonal function, so that disruption of their metabolism by diabetes results in the accumulation of neurotoxic intermediates and compromises production of neuronal support factors, contributing to axonal degeneration, endothelial dysfunction and diabetic neuropathy. Abstract | The prevalence of diabetes worldwide is at pandemic levels, with the number of patients increasing by 5% annu...

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Section: Box 3 | Satellite Glial Cellsmentioning

confidence: 99%

Schwann cell interactions with axons and microvessels in diabetic neuropathy

et al. 2017

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“…T REG are currently little investigated in IBS, with only one report showing that numbers and suppressive capabilities of blood and colon T REG are unaltered in IBS ( 98 ). Th e T H 17 axis is also yet to be studied in detail, and although the functions of T H 17 cytokines in intestinal homeostasis are controversial IL-17 has been shown to sensitize sensory nerves in the somatosensory system ( 99,100 ). Understanding the role and relationship of these cell types is currently of great interest in a number of infl ammatory disease states, such as infl ammatory bowel disease ( 101 ), but is also very likely to provide vital information regarding the maintenance of the low grade but chronic immune activation observed in IBS patients.…”

Section: -Htmentioning

confidence: 99%

Immune Activation in Irritable Bowel Syndrome: Can Neuroimmune Interactions Explain Symptoms?

Hughes

Zola

et al. 2013

American Journal of Gastroenterology

133

117

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Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal (GI) tract characterized by pain or discomfort from the lower abdominal region, which is associated with altered bowel habit. Despite its prevalence, there is currently a lack of effective treatment options for patients. IBS has long been considered as a neurological condition resulting from alterations in the brain gut axis, but immunological alterations are increasingly reported in IBS patients, consistent with the hypothesis that there is a chronic, but low-grade, immune activation. Mediators released by immune cells act to either dampen or amplify the activity of GI nerves. Release of a number of these mediators correlates with symptoms of IBS, highlighting the importance of interactions between the immune and the nervous systems. Investigation of the role of microbiota in these interactions is in its early stages, but may provide many answers regarding the mechanisms underlying activation of the immune system in IBS. Identifying what the key changes in the GI immune system are in IBS and how these changes modulate viscerosensory nervous function is essential for the development of novel therapies for the underlying disorder.

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“…IL-17 is a pro-inflammatory cytokine predominantly produced by Th17 cells, but also by neutrophils, cytotoxic T cells and glial cells and has important role in nervous system inflammatory disorders such as multiple sclerosis 7,8 . IL-17 administration in laboratory rats has induced pain behavior 63 . After nervous injury, IL-17 increases nervous degeneration with peak around the seventh day and is found in T cells of the injured nerve 62 .…”

Section: Other Inflammatory Cytokinesmentioning

confidence: 99%

“…After nervous injury, IL-17 increases nervous degeneration with peak around the seventh day and is found in T cells of the injured nerve 62 . Pain and hypersensitivity are decreased in rats with Rag type 1 defficiency (family of restriction endonuclease enzymes which cleave DNA by recognizing the site by the identification of bases pairs sequences) in T cells, with failure in Il-17 and IL-17 expression in rats 63,64 . This effect decreases both T cells and macrophages infiltrate in sciatic nerve decreasing spinal cord glial activity 63 .…”

Section: Other Inflammatory Cytokinesmentioning

confidence: 99%

“…Pain and hypersensitivity are decreased in rats with Rag type 1 defficiency (family of restriction endonuclease enzymes which cleave DNA by recognizing the site by the identification of bases pairs sequences) in T cells, with failure in Il-17 and IL-17 expression in rats 63,64 . This effect decreases both T cells and macrophages infiltrate in sciatic nerve decreasing spinal cord glial activity 63 . This way, there are increasing evidences that IL-17 is involved in NP maintenance.…”

Section: Other Inflammatory Cytokinesmentioning

confidence: 99%

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