Researchers at Oregon Health & Science University and the Portland Veterans Affairs Medical Centre have found that estrogen, produced in high volumes during pregnancy, boosts the expression and number of regulatory cells that are key to fighting Multiple Sclerosis (MS) and other autoimmune diseases, such as arthritis and diabetes.
The study, published in the "Cutting Edge" section of the current issue of The Journal of Immunology, shows the hormone augments a compartment containing T cells known as CD4+CD25+, and a regulatory protein called FoxP3. The cells are important for protecting mice against a model for human MS called experimental autoimmune encephalomyelitis (EAE).
Autoimmune disease has been associated with a deficiency of FoxP3, whose expression is a reliable indicator of the regulatory T cells' function and development.
"This is the first report that this single, benign compound - estrogen - can increase regulatory cells," said study co-author Halina Offner, professor of neurology, and anesthesiology and peri-operative medicine, OHSU School of Medicine and the Portland VA Medical Centre. "When you remove (the CD4+CD25+ cells), animals get autoimmune disease. They're very important to maintaining a healthy state," he added.
Dennis Bourdette, professor and chairman of neurology, OHSU School of Medicine, and director of OHSU's MS Centre of Oregon, says understanding how estrogens boost protective T cells to fight MS will lead to the development of "estrogen-like" drugs that could increase the cells without the female hormone's side effects.
The study found that estrogen treatment simulates pregnancy in increasing T cell levels. It also demonstrated that estrogen boosts expression of the FoxP3 protein not only in a mouse model, but also in cell culture. "In vitro, estrogen can induce regulatory cells," Halina Offner said.
In their research, the OHSU-VAMC scientists saw a "significant increase" in the number of CD4+CD25+ regulatory T cells - 43 per cent - and a correlated boost in FoxP3 expression in mice treated for 14 days with estrogen versus untreated mice. Pregnancy increased the CD4+CD25+ count and amplified FoxP3 expression as well.
Estrogen levels during pregnancy can be 50 to 100 times higher than normal, Offner said. Scientists attribute this jump to the body's natural defense against its own immune system, whose reaction to self-antigen proteins, or "self-Ags," in fetal tissue can lead to fetal rejection, as well as the chronic inflammation that is the root of autoimmune disease.
Offner said, however, long-term estrogen therapy has potential side effects, and developing estrogen-like drugs can help patients avoid these potentially detrimental effects.
Research is continuing on regulatory T cells - "T-regs," as they're often called - and their potential benefit for other autoimmune diseases, Offner said.
The study was supported by grants from the National Institutes of Health, the National Multiple Sclerosis Society, the Nancy Davis MS Centre Without Walls, the Department of Veterans Affairs, the American Diabetes Association and the Juvenile Diabetes Research Foundation.