Targeting the chemokine receptor CXCR6, a protein at the surface of a certain group of T helper cells, prevented the development of multiple sclerosis (MS) in a mouse model of the disease, a study reports.
Its findings suggest that antibodies targeting T helper cells — known drivers of MS — that carry the CXCR6 receptor may slow or prevent MS progression without broadly dampening the immune system.
The study “SerpinB1 controls encephalitogenic T helper cells in neuroinflammation” was published in the journal PNAS.
Immune CD4 positive T-cells, known as T helper cells, play an important role in the autoimmune reaction against myelin (the protective coat surrounding neurons), the hallmark of MS. These cells are characterized by high levels of two pro-inflammatory molecules, called IL1β and IL-23, that help to sustain the immune reaction. However, the mechanisms through which these autoreactive cells arise is still unclear.
Researchers at the Boston Children’s Hospital discovered a link between IL-23 and a protein called SerpinB1 (Sb1) that helps autoreactive T-cells escape suicide and expand uncontrollably.
They first observed that in mice with experimental autoimmune encephalomyelitis (EAE), a condition that mimics key pathological features of MS in humans, a subset of CD4 positive T-cells had high levels of Sb1, along with Rorc and IL17a, two inflammatory factors.
Researchers then tested how Sb1 affects the autoreactivity of T-cells. Deleting the Sb1 gene from T helper cells led to a significant decrease in the cell’s ability to infiltrate the spinal cord, lessening EAE symptoms.
A genetic screening of T-cells derived from mice without the Sb1 gene revealed that these cells were lacking the chemokine receptor CXCR6. Right away, the team saw an opportunity to use this marker as a way to target these cells.
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