Regulatory T cells play an important role in the immune system: They rein in wayward T cells that attack normal tissues in the body, causing autoimmune diseases like multiple sclerosis. Now a University of Edinburgh-led team has uncovered a mechanism in multiple sclerosis that prevents regulatory T cells from developing.
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, or Tregs. Tregs curb inflammation and stop the immune system from attacking the body’s own tissues. In the case of MS, immune cells attack myelin, a fatty substance that coats and protects nerve cells.
Siobhan Ni Choileain and her colleagues pinpointed a “glitch” in the T cells of MS patients that sabotaged the processing of the protein CD46, which controls the conversion of helper T cells into Tregs. In healthy cells, the stimulation of a T-cell receptor led to the glycosylation of CD46, which did not happen in cells isolated from MS patients, they found.
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The findings, which appear in Science Signaling, may explain why this pathway is faulty in patients with MS and provide clues as to how the disease develops. They could inspire the development of immunotherapies against the neurodegenerative disease.
Simply delivering Tregs to the body to fight MS is an attractive, but not very long-lasting, treatment. So targeting the immune response itself would be ideal. In another approach, researchers led by the University of Florida created a gene therapy, delivered to the liver, that stimulates Tregs to tamp down on self-reactive T cells, 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.
Jumpstarting Treg activity is a hot area in autoimmune research, with Celgene and Eli Lilly both splashing big bucks on Treg stimulators. In January, Celgene dropped $300 million on Delinia, whose lead candidate could be used to target autoimmune conditions such as lupus and rheumatoid arthritis. And in July, Lilly forked over $150 million up front to co-develop a Treg booster with Nektar Therapeutics. Nektar stands to reel in another $100 million in development and regulatory milestones.