Scientists at the National Institutes of Health's National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) report important new findings related to the control of autoimmune T cells. Their discoveries, described in the journal Immunity, have largely to do with a cytokine, or chemical messenger, called interleukin-2 (IL-2) and its role in the normal balance of the body's immune-regulating T cells. IL-2 has long been used to grow T cells in the laboratory, yet mice that lack IL-2 die from autoimmune disease. Researchers led by NIAMS Scientific Director John O'Shea, M.D., have found that IL-2 inhibits autoimmunity by acting on different T cells with opposing functions.
However, emerging evidence indicates that the development of autoimmunity is controlled by two additional subsets of T cells. One subset, called regulatory T cells (T regs), has critical immunosuppressive functions, and IL-2 promotes the generation of this lineage. More recently, a third subset of T helper cells, Th17, has come to light. Th17s produce an inflammatory cytokine called interleukin-17 (IL-17), and Th17 cells appear to be very important in driving autoimmune disease. For some time, mice lacking IL-2 have been recognized as a model of autoimmunity. This was thought to be due to impairment in T regs; however, the present work reveals that another aspect of their immunity is that they have large numbers of Th17s. Perhaps the most exciting new finding is that IL-2 seems to inhibit autoimmunity not only by promoting the production of regulatory T cells, but simultaneously inhibiting Th17 cells. "You can think of it as these two poles," says Dr. O'Shea. "There are these inflammatory cells called Th17s that promote autoimmunity, and there are these other cells, T regs, that inhibit autoimmunity." It is clear now that IL-2 inhibits autoimmunity by acting on both types of cells.
Dr. O'Shea says it's premature to suggest that administering IL-2 might be a way to control Th17 and thus autoimmunity. "More important in the short term is to understand how these cells are generated in the course of the diseases, what factors are driving the differentiation of these cells. That is really more what this paper is all about," he says.
"In the future, if we could learn how to regulate the balance between Th17 and T regs, if we could do that therapeutically with cytokines or anticytokines, that would be great for patients."
Other NIH institutes involved in this research were the National Institute of Allergy and Infectious Diseases and the National Institute of Diabetes and Digestive and Kidney Diseases.
This work was also supported by the National Institute of Diabetes and Digestive and Kidney Diseases.
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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Laurence A, et al. Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity 2007;26(3):371-381.