IL-17A is increased in the serum and in spinal cord CD8 and mast cells of ALS patients

Fiala, Milan; Chattopadhay, Madhuri; Cava, Antonio La; Tse, Eric; Liu, Guanghao; Lourenço, Elaine; Eskin, Ascia; Liu, Philip T.; Magpantay, Larry; Tse, Stephen; Mahanian, Michelle; Weitzman, Rachel; Tong, Jason; Nguyen, Caroline; Cho, Tiffany; Koo, Patrick; Sayre, James W.; Martı́nez-Maza, Otoniel; Rosenthal, Mark J.; Wiedau‐Pazos, Martina

doi:10.1186/1742-2094-7-76

Cited by 152 publications

(139 citation statements)

References 48 publications

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“…Most importantly, many of these immune changes in the animal model have been confirmed in patients with nonhereditary ALS [24,70,99,100,131,132]. Henkel et al [133] demonstrated that in patients with rapidly progressing clinical states, an inverse correlation was seen between Treg numbers in the blood and leukocyte levels of FoxP3, a transcription factor required for Treg suppressive function [134].…”

Section: Neuroinflammation In Patients With Als: Tregsmentioning

confidence: 98%

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Protective and Toxic Neuroinflammation in Amyotrophic Lateral Sclerosis

et al. 2015

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Amyotrophic lateral sclerosis (ALS) is a clinically heterogeneous disorder characterized by loss of motor neurons, resulting in paralysis and death. Multiple mechanisms of motor neuron injury have been implicated based upon the more than 20 different genetic causes of familial ALS. These inherited mutations compromise diverse motor neuron pathways leading to cell-autonomous injury. In the ALS transgenic mouse models, however, motor neurons do not die alone. Cell death is noncell-autonomous dependent upon a well orchestrated dialogue between motor neurons and surrounding glia and adaptive immune cells. The pathogenesis of ALS consists of 2 stages: an early neuroprotective stage and a later neurotoxic stage. During early phases of disease progression, the immune system is protective with glia and T cells, especially M2 macrophages/microglia, and T helper 2 cells and regulatory T cells, providing anti-inflammatory factors that sustain motor neuron viability. As the disease progresses and motor neuron injury accelerates, a second rapidly progressing phase develops, characterized by M1 macrophages/microglia, and proinflammatory T cells. In rapidly progressing ALS patients, as in transgenic mice, neuroprotective regulatory T cells are significantly decreased and neurotoxicity predominates. Our own therapeutic efforts are focused on modulating these neuroinflammatory pathways. This review will focus on the cellular players involved in neuroinflammation in ALS and current therapeutic strategies to enhance neuroprotection and suppress neurotoxicity with the goal of arresting the progressive and devastating nature of ALS.

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Section: Neuroinflammation In Patients With Als: Tregsmentioning

confidence: 98%

“…Understanding the role of Tregs play in neurodegeneration has spread, encompassing many different neurodegenerative diseases, including ALS [51,98]. The role of Th17 is less well defined in the mSOD1 transgenic animal, but evidence from patients with ALS supports their involvement in the neuroinflammatory process [98][99][100][101].…”

Section: T Lymphocytesmentioning

confidence: 99%

Protective and Toxic Neuroinflammation in Amyotrophic Lateral Sclerosis

et al. 2015

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“…[59] Th17 cells are crucial for the development of certain autoimmune diseases, exhibiting neurodestructive effects in neuroinflammatory diseases. [60] In ALS patients, elevated IL-17 and Th17-related cytokines (IL-6, TNF-α, IL-1 and IL-23) [61][62][63] have been observed. However, the contribution of Th17 cells in promoting ALS development has not been established yet because of two challenges: late diagnosis and chronic disease.…”

Section: Th17 Cells Nerve Injury and Alsmentioning

confidence: 99%

How are necroptosis, immune dysfunction, and motoneuron death connected in amyotrophic lateral sclerosis?

Liu¹,

Zheng²,

Xin³

et al. 2017

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How to cite this article: Liu JF, Zheng OX, Xin JG, Chen HH, Xin JJ. How are necroptosis, immune dysfunction, and motoneuron death connected in amyotrophic lateral sclerosis ? Neuroimmunol Neuroinflammation 2017;4:109-16. Abnormal immune response/inflammation is present in patients of amyotrophic lateral sclerosis (ALS). Autoimmune-related inflammation has been thought to be involved in the pathogenesis of ALS. However, how the abnormal immune responses are initiated, what specific immune cells and how these immune cells are involved in this disease have not been well understood. This is partly owing to two facts of ALS: late diagnosis and chronic nature. The late diagnosis makes it difficult to conclude whether the abnormal immune responses/inflammation is the cause or result of the disease. The chronic nature makes it difficult to determine the best timing for the detection of such autoimmune responses. To resolve these two challenges for research, the authors introduced motor nerve injury (facial nerve axotomy, FNA) into a pre-symptomatic mouse ALS model (8-week-old SOD1 G93A mice), which induces a readily detectable immune response in a predictable time period (3-14 days). The authors found that pre-symptomatic SOD1 G93A mice showed a higher basal level of T cell activation and Th17 cells than WT mice, which can be further increased by FNA. However, why these pro-inflammatory Th lymphocyte MinireviewThis is an open access article distributed under the terms of the Creative Commons AttributionNonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

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“…The main histopathological feature of inflammation is the proliferation of reactive astrogliosis and of activated microglial cells, associated with alterations in their cellular functions, such as glutamate reuptake failure and release of proapoptotic and proinflammatory factors (Sanagi et al, 2010;Sargsyan et al, 2005;Sofroniew, 2005). Molecules associated with inflammatory process, such as interleukins 6, 12, 15, 17A, 23, C4d and C3d complement proteins, as well as tumor necrosis factor-alpha, have been found in blood and CSF from ALS patients (Almer et al, 2002;Fiala et al, 2010;Henkel et al, 2004;Kawamata et al, 1992;McGeer et al, 1991;Moreau et al, 2005;Rentzos et al, 2010a, b). The finding of increased levels of granzymes A, B in serum (Ilzecka, 2011) and decrease in cytochrome c levels in the CSF (Ilzecka, 2007), suggests an apoptotic process in human disease.…”

Section: Inflammationmentioning

confidence: 99%