Scientists in the Molecular Immunology and Inflammation Branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and their colleagues have discovered how retinoic acid signaling can promote or suppress the activity of helper T cells, a class of immune cells involved in inflammatory responses.
Understanding how the newly discovered mechanism regulates the balance between two kinds of helper T cells - pro-inflammatory Th17 cells and anti-inflammatory T regulatory cells - could eventually yield benefits for people with autoimmune disease. The work, which appeared in the February 2008 issue of Blood , was a collaborative effort of NIAMS, the National Institute of Allergy and Infectious Diseases and the Howard Hughes Medical Institute.
Helper T cells play a critical role in the delicate balance between the immune system's normal defense of the body from infection and immune system overactivity, which results in mistaken attacks on the body's own cells and can sometimes produce autoimmune disease.
In their research, NIAMS' John O'Shea, M.D., Arian Laurence, Ph.D., and their colleagues explored chemicals and hormones that alter the balance between Th17 and T regulatory cells in mice. They learned that one such chemical is retinoic acid, a byproduct of vitamin A. Specifically, the group showed that retinoic acid inhibited the formation of the pro-inflammatory Th17 cells and promoted the production of the anti-inflammatory T regulatory cells. Conversely, they found that using an inhibitor of retinoic acid reduced the production of T regulatory cells, suggesting that T regulatory cells do, in fact, depend upon this vitamin A byproduct.
How retinoic acid alters the balance is not fully understood, but the researchers concluded that it most likely binds to and activates a protein within the cell to change the way it matures.
Retinoic acid supplementation is currently used to treat a wide variety of illnesses, from skin complaints such as acne to certain types of leukemia. The NIAMS team is interested in its potential to treat inflammatory diseases. Understanding and possibly controlling Th17 and T regulatory cells, say the scientists, could also result in new insights into the development of autoimmune diseases. The researchers speculate that if these two helper T cell types can be manipulated in humans, it is possible that the inflammation and tissue destruction of autoimmune diseases could be slowed or halted. In fact, retinoic acid and related drugs have already been shown to be effective in animal models of some such disorders.
The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at 301-495-4484 or 877-22-NIAMS (free call) or visit the NIAMS Web site at http://www.niams.nih.gov .
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Elias K, et al. Retinoic acid inhibits Th17 polarization and enhances FoxP3 expression through a Stat-3/Stat-5 independent signaling pathway. Blood2008;111:1013-1020.