Deficiency of Socs3 leads to brain-targeted EAE via enhanced neutrophil activation and ROS production.

08:00 EDT 2nd April 2019 | BioPortfolio

Summary of "Deficiency of Socs3 leads to brain-targeted EAE via enhanced neutrophil activation and ROS production."

Dysregulation of the JAK/STAT signaling pathway is associated with Multiple Sclerosis (MS) and its mouse model, Experimental Autoimmune Encephalomyelitis (EAE). Suppressors Of Cytokine Signaling (SOCS) negatively regulate the JAK/STAT pathway. We previously reported a severe, brain-targeted, atypical form of EAE in mice lacking Socs3 in myeloid cells (Socs3ΔLysM), which is associated with cerebellar neutrophil infiltration. There is emerging evidence that neutrophils are detrimental in the pathology of MS/EAE, however, their exact function is unclear. Here we demonstrate that neutrophils from the cerebellum of Socs3ΔLysM mice show a hyper-activated phenotype with excessive production of reactive oxygen species (ROS) at the peak of EAE. Neutralization of ROS in vivo delayed the onset and reduced severity of atypical EAE. Mechanistically, Socs3-deficient neutrophils exhibit enhanced STAT3 activation, a hyper-activated phenotype in response to G-CSF, and upon G-CSF priming, increased ROS production. Neutralization of G-CSF in vivo significantly reduced the incidence and severity of the atypical EAE phenotype. Overall, our work elucidates that hypersensitivity of G-CSF/STAT3 signaling in Socs3ΔLysM mice leads to atypical EAE by enhanced neutrophil activation and increased oxidative stress, which may explain the detrimental role of G-CSF in MS patients.


Journal Details

This article was published in the following journal.

Name: JCI insight
ISSN: 2379-3708


DeepDyve research library

PubMed Articles [23746 Associated PubMed Articles listed on BioPortfolio]

Radiotherapy resistance acquisition in Glioblastoma. Role of SOCS1 and SOCS3.

Glioblastoma multiforme (GBM) is a poor prognosis type of tumour due to its resistance to chemo and radiotherapy. SOCS1 and SOCS3 have been associated with tumour progression and response to treatment...

Circulating neutrophil extracellular traps and neutrophil activation are increased in proportion to disease severity in human malaria.

Neutrophil activation results in Plasmodium parasite killing in vitro, but neutrophil products including neutrophil extracellular traps (NETs) mediate host organ damage and may contribute to severe ma...

Therapeutic Targeting of Neutrophil Extracellular Traps in Atherogenic Inflammation.

Neutrophils and neutrophil extracellular traps (NETs) have a robust relationship with atherothrombotic disease risk, which led to the idea that interfering with the release of NETs therapeutically wou...

Garcinia Multiflora Inhibits FPR1-Mediated Neutrophil Activation and Protects Against Acute Lung Injury.

Formyl peptide receptors (FPRs) recognize different endogenous and exogenous molecular stimuli and mediate neutrophil activation. Dysregulation of excessive neutrophil activation and the resulting imm...

SIRT5 deficiency suppresses mitochondrial ATP production and promotes AMPK activation in response to energy stress.

Sirtuin 5 (SIRT5) is a member of the NAD+-dependent sirtuin family of protein deacylase that catalyzes removal of post-translational modifications, such as succinylation, malonylation, and glutarylati...

Clinical Trials [10926 Associated Clinical Trials listed on BioPortfolio]

Impact of Neutrophil Activation in Acute Ischemic Stroke Patients Treated With Endovascular Therapy

Clinical and experimental data suggest that neutrophil activation and extravasation are deleterious in acute ischemic stroke (AIS) involving an increased risk of unfavorable outcome and he...

Effect of Spinal or Sevoflurane Anesthesia on Neutrophil Activation During Knee Surgery With Pneumatic Tourniquet

Aim of study : Assessement of neutrophil activation during ischemia reperfusion associated with tourniquet use for total knee arthroplasty. This activation was compared in a group of patie...

Endotoxin, Neutrophil Function and Albumin in Renal Insufficiency

Chronic kidney disease is widespread in the western world with bacterial infection and sepsis as common complication. It has been shown that innate immune defence, represented by dysfuncti...

Measurement of Smoking−Induced Neutrophil Activation

Neutrophil involvement in the development of COPD by smokers is well recognised. However not all smokers develop overt lung disease. We have previously shown that uptake of FDG is related ...

Neurofeedback for Stroke Rehabilitation

Real-time neurofeedback aims to alter brain activation patterns through online feedback of ongoing brain activity using magnetic resonance imagining (MRI). Stroke survivors will be randomi...

Medical and Biotech [MESH] Definitions

The process in which the neutrophil is stimulated by diverse substances, resulting in degranulation and/or generation of reactive oxygen products, and culminating in the destruction of invading pathogens. The stimulatory substances, including opsonized particles, immune complexes, and chemotactic factors, bind to specific cell-surface receptors on the neutrophil.

A glycosidase that hydrolyzes a glucosylceramide to yield free ceramide plus glucose. Deficiency of this enzyme leads to abnormally high concentrations of glucosylceramide in the brain in GAUCHER DISEASE. EC

An absence or deficiency in PROTEIN C which leads to impaired regulation of blood coagulation. It is associated with an increased risk of severe or premature thrombosis. (Stedman's Med. Dict., 26th ed.)

A glycoprotein secreted by the cells of the GASTRIC GLANDS that is required for the absorption of VITAMIN B 12 (cyanocobalamin). Deficiency of intrinsic factor leads to VITAMIN B 12 DEFICIENCY and ANEMIA, PERNICIOUS.

Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (IMMUNOTOXINS) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (see RADIOTHERAPY).

Quick Search


DeepDyve research library

Relevant Topics

Spinal Cord Disorders
The spinal cord is a bundle of nerves that runs down the middle of the back which carry signals back and forth between the body and brain. It is protected by vertebrae, which are the bone disks that make up the spine. An accident that damages the verte...

Multiple Sclerosis MS
Multiple sclerosis (MS) is the most common disabling neurological condition affecting 100,000 young adults in the UK. The condition results from autoimmune damage to myelin, causing interference in nerve signaling. Symptoms experienced depend on the pa...

Searches Linking to this Article