Researchers have identified a new type of white blood cell that can suppress T-cell hyperactivity in experimental autoimmune encephalomyelitis (EAE), an animal model used to study multiple sclerosis (MS) and other human diseases that affect the central nervous system. Moreover, the group found that these blood cells were prominent in patients who responded to interferon-beta (IFN-β) treatment for MS. The results were published in the journal Nature Medicine on February 16, 2014.
The defective generation or function of white blood cells called regulatory T-cells (T-reg cells) in autoimmune disease contribute to chronic inflammation found in diseases such as MS, EAE, and various types of tissue injury. Yawei Liu, and co-workers at BRIC, the University of Copenhagen, have discovered a group of T-cells that after ectopic expression of the FoxA1 gene, confer suppressive properties in a newly identified T-reg cell population named FoxA1+ T-reg cells. Development of these FoxA1+ T-reg cells occurs primarily in the central nervous system in response to autoimmune inflammation. The group discovered that ectopic FoxA1 expression generates FoxA1+ T-reg cells that suppress T-cells by inducing activated apoptosis, programmed cell death. The FoxA1+ T-reg cells were adoptively transferred in mice and showed to inhibit EAE. The researchers also found that the development of FoxA1+ T-reg cells is induced by the cytokine, IFN-β, and requires IFN-α/β receptor (Ifnar) signaling. This was concluded because the frequency of FoxA1+ T-reg cells was reduced in mice lacking the receptor. Lastly, Yawei Liu, and co-workers discovered that patients with relapsing-remitting MS who exhibited a clinical response to treatment with IFN-β were associated with an increased frequency of the newly discovered FoxA1+ T-reg cells in the blood.
The number of people around the world affected by MS is reported at 2.3 million, an increase in 10 percent over the past five years. Currently, no curing treatment exists for the disease. The studies presented here provide the potential for the development of new therapeutic options for MS patients not benefiting from existing drugs. This is especially true for patients suffering from the more chronic and progressive forms of MS. In addition to MS, these results may lead to better treatments for other autoimmune diseases that are associated with chronic inflammation including types of diabetes, inflammatory bowel disease and rheumatoid arthritis.