Spotlight on Research 2008

June 2008 (historical)

New Pathway Shows Promise for Tempering Inflammatory Response

Scientists at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) have discovered how a cell-signaling protein, or cytokine, called interleukin 10 (IL-10) is secreted to suppress the immune system in response to the inflammation produced by autoimmune diseases. The discovery of this mechanism could produce new insights into such disorders and their potential treatments. The work appeared a recent issue of Nature Immunology .

Mice unable to produce IL-10 have been shown to develop a fatal autoimmune disease, a condition in which an overactive immune system mistakenly attacks the body's own tissues. Although the importance of IL-10 in immunosuppression has been recognized, how the cytokine is produced as a response to excessive inflammation has been unclear. Now, researchers under the direction of Christopher Hunter, Ph.D., at the University of Pennsylvania School of Veterinary Medicine and NIAMS Scientific Director John O'Shea, M.D., have discovered that two other cytokines, IL-27 and IL-6, prompt immune cells called T cells to secrete IL-10.

Specifically, Hunter and O'Shea's groups determined that in the newly identified pathway, cytokines IL-27 and IL-6 play roles in stimulating T helper type 1 and type 2 cells, along with a recently identified type of T helper cell (Th17), to produce IL-10. T helper cells relay stimulatory signals that activate other immune cells. By producing IL-10 and other cytokines, T helper cells orchestrate the body's immune responses and modulate its responses to infectious organisms.

The stimulatory effect of IL-27 and IL-6 in the pathway was dependent on transcription factors STAT 1 and STAT 3, for IL-27, and STAT 3, for IL-6. Transcription factors are proteins that influence gene expression.

"Production of IL-10 by T cells is a critical way in which immune responses are held in check," said O'Shea. "If we can tease out the intricacies of the regulation of IL-10 and other cytokines, we may be better able to see how autoimmune diseases develop and design possible treatments for those they affect."

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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Stumhofer J, et al. Interleukins 27 and 6 induce STAT3-mediated T cell production of interleukin 10. Nature Immunology 2007;8(12):1363-1371.