T lymphocytes potentiate endogenous neuroprotective inflammation in a mouse model of ALS

Chiu, Isaac M.; Chen, Adam; Zheng, Yi; Kosaras, Béla; Tsiftsoglou, Stefanos A.; Vartanian, Timothy; Brown, Robert H.; Carroll, Michael

doi:10.1073/pnas.0804610105

Cited by 312 publications

(338 citation statements)

References 37 publications

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“…Nonetheless, it appears that mSOD1 T‐cells are not functionally impaired 57, 58, 61. Contrastingly, B‐cells were not found to be present in the spinal cords of ALS mouse models and complete ablation of B‐cells did not change the disease phenotype 56, 57, 62…”

Section: Status Of Neuroinflammation In Als and Smamentioning

confidence: 93%

“…However, under pathological circumstances, they can infiltrate the spinal cord 55. In the mSOD1 mouse model, T‐cells infiltrate the spinal cord at a time point associated with microglial activation, highlighting the potential synergy of these cells in disease in a mouse model of ALS 56, 57, 58. In this context, T‐cells appear particularly protective 56, 57.…”

Section: Status Of Neuroinflammation In Als and Smamentioning

confidence: 97%

“…In the mSOD1 mouse model, T‐cells infiltrate the spinal cord at a time point associated with microglial activation, highlighting the potential synergy of these cells in disease in a mouse model of ALS 56, 57, 58. In this context, T‐cells appear particularly protective 56, 57. Importantly, hybridizing RAG2 −/− onto the mSOD1 mice, creating ALS mice without any T‐cells or B‐cells, lead to severe worsening of disease progression 57.…”

Section: Status Of Neuroinflammation In Als and Smamentioning

confidence: 99%

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New insights into SMA pathogenesis: immune dysfunction and neuroinflammation

Deguise

Kothary

2017

Ann Clin Transl Neurol

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Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by motor neuron degeneration, although defects in multiple cell types and tissues have also been implicated. Three independent laboratories recently identified immune organ defects in SMA. We therefore propose a novel pathogenic mechanism contributory to SMA, resulting in higher susceptibility to infection and exacerbated disease progression caused by neuroinflammation. Overall, compromised immune function could significantly affect survival and quality of life of SMA patients. We highlight the recent findings in immune organ defects, their potential consequences on patients, our understanding of neuroinflammation in SMA, and new research hypotheses in SMA pathogenesis.

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Section: Status Of Neuroinflammation In Als and Smamentioning

confidence: 93%

Section: Status Of Neuroinflammation In Als and Smamentioning

confidence: 97%

Section: Status Of Neuroinflammation In Als and Smamentioning

confidence: 99%

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New insights into SMA pathogenesis: immune dysfunction and neuroinflammation

Deguise

Kothary

2017

Ann Clin Transl Neurol

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“…Other and our groups have showed that CD4 + T cells mediate anti-inflammatory effect after nerve injury as well as in ALS disease; however it is in context-and subsetdependent manner. [53][54][55][56] It is generally thought that beneficial effects of CD4 + T cells are mainly mediated by its anti-neuroinflammatory subsets, such as Treg and Th2 cells [56,57] and that detrimental effects are mediated by pro-inflammatory CD4 + T subsets, such asTh1 and Th17 cells. The differential development of CD4 + T subset is determined by both CD4 + T cells and their cytokine environment.…”

Section: Environment-dependent Function Of Cd4 + T Cells In Alsmentioning

confidence: 99%

“…[51,52] Consistent with this notion, knockout of CD4 + T cells in SOD1 G93A mice resulted in exacerbation of ALS-like symptoms and a decreased life span. [53,54] Collectively, it appears that CD4 + T cell-mediated regulation determines the direction and nature of immune responses in ALS, and an ideal immune-based therapy for ALS should be able to inhibit the "detrimental" effects of immune cell without simultaneously comprising the "beneficial" functions. Therefore, it is necessary to identify the specific subsets of immune cells and to elucidate how they are involved in the pathogenesis of ALS.…”

Section: Necroptosis and Immune Dysfunctionmentioning

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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