Newly Discovered Dysfunction in T-cell Development Sheds Light on Multiple Sclerosis

Autoimmune diseases are caused by immune system over-activity, which is when the body attacks and damages its own tissues. In the autoimmune disease, multiple sclerosis (MS), the immune system attacks myelin, the fatty substance that coats and protects nerve fibers in the brain and spinal cord. While the exact causes of autoimmune disease remain unclear, scientists know that these diseases, ranging from MS to asthma, have something in common—the failure of helper T-cells to develop into regulatory T-cells, also known as Tregs. Tregs ameliorate inflammation and stop the immune system from attacking the body’s own tissues.

A research team from the University of Edinburgh has now uncovered a mechanism in MS that prevents these Tregs from developing. Authors of the study (Choileain et al) have discovered that the stimulation of T-cell receptors that leads to the processing of the protein CD46—something healthy cells do— does not occur in patients with MS. These findings might explain why this dysfunction occurs in patients with MS, which could lead to the development of immunotherapies against MS, and perhaps other immune disorders.

In another study, researchers from the University of Florida created a gene therapy that stimulates Tregs to curb self-reactive effector T-cells, thereby protecting myelin. They used an adeno-associated virus as a vehicle for the therapy and found that it delayed progression and reversed symptoms of early- stage MS in mice.

Jump-starting Treg activity is a hot area in autoimmune research. Companies like Celgene and Eli Lilly are investing a lot of money into research on Treg stimulators that can be used to target other autoimmune conditions such as lupus and rheumatoid arthritis.

SOURCE: Al Idrus A. Gene therapy reverses symptoms, slows progression of MS in mice. FierceBiotech site. Sep 21, 2017. symptoms-slows-progression-ms-mice. Accessed February 23, 2018. NHR

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