Targeting the excessive activation of immune cells called neutrophils, and the associated oxidative stress, may be a therapeutic strategy in patients with multiple sclerosis (MS), according to a mouse study.
The study, “Deficiency of Socs3 leads to brain-targeted EAE via enhanced neutrophil activation and ROS production,” was published in the journal JCI Insight.
Neutrophils are the most common type of white blood cells, and are the first responders to foreign antigens or inflammation. Accordingly, their levels increase in response to infections and injuries.
Neutrophils have been implicated in MS and other autoimmune diseases, but their precise role is not entirely clear.
Prior work in a severe mouse model of MS, called atypical experimental autoimmune encephalomyelitis (EAE), showed that disease processes are driven by neutrophils. These mice typically show damage in the cerebellum, a brain area with a major role in the control of motor coordination, balance, and speech.
Previous research also revealed that a cell signaling pathway known as JAK/STAT is dysregulated in MS and in the EAE model, and that an inflammatory molecule called the granulocyte colony-stimulating factor (G-CSF) — key for the maturation of neutrophils — is associated with disability, relapses, and lesion burden in MS patients.
Now, a team at the University of Alabama at Birmingham used the atypical EAE mouse model to study the role of neutrophils in MS.
For this purpose, the Socs3 gene in the mice was deleted, leading to an overly active STAT3 protein — one of the components of the JAK/STAT pathway — and neutrophil infiltration in the cerebellum. Exaggerated activation of STAT3 has been observed in immune cells from MS patients, and correlates with disease progression.
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