IL-17 — A Central Regulator of Inflammation and Autoimmunity?
Cytokines are chemical signaling molecules that transfer information from cell to cell. Many cytokines work together to regulate the immune system. Intense interest has focused on interleukin-17 (IL-17). This cytokine seems to be important in many inflammatory diseases, including rheumatoid arthritis, multiple sclerosis, asthma and systemic lupus erythematosus. IL-17 promotes inflammation by activating cells to produce more pro-inflammatory cytokines.
What Problem Was Studied?
In previous experiments, researchers found that the source of IL-17 and a closely related cytokine, IL-17F, is a particular T helper cell called the inflammatory T helper (THi) cell. Arthritis Foundation-funded researcher Seon Hee Chang, PhD, and his colleague Chen Dong, PhD, from the MD Anderson Cancer Center in Houston, have been investigating THi and the cytokines these cells release. Their experiments were designed to determine where IL-17 and other members of that cytokine family go and what they do.
What Was Done in the Study?
THi cells were generated from isolated T cells. The cytokines they secreted were analyzed and described. Since the authors were aware that IL-17 and IL-17F are similar in nature, both are produced by the same cells and both enhance inflammation, they reasoned that these two cytokines might interact with each other.
What Were the Study Results?
It previously was shown that THi cells release these particular cytokines not as single molecules, but as molecular pairs, called dimers. Two molecules of IL-17 or two molecules of IL-17F normally bind together to form homodimers. What surprised the researchers was that one IL-17 and one IL-17F could also bind together to form a heterodimer, which they named IL-17A/F. This pairing of the two forms of IL-17 represents a new cytokine molecule that has not been described before.
The team was able to conduct additional experiments to determine that IL-17A/F is biologically active and regulates inflammatory responses in the body. The heterodimer activates fibroblasts and macrophages to produce other pro-inflammatory mediators.
What Does This Mean to People with Arthritis?
Drs. Chang and Dong advise that future studies are needed to understand how these homodimers and heterodimers affect the development and progression of human diseases. They do however conclude, “These results reveal a novel mechanism whereby T cells regulate inflammatory responses. Considering the similar actions of IL-17, IL-17F and IL-17A/F, it may be beneficial to target all of them in many inflammatory diseases that now have been found to be mediated by THi cells.” In other words, scientists are looking for ways to block the powerful effects of IL-17 family members in promoting inflammation. They will have to keep in mind that several different members of the IL-17 family will need to be considered when new drugs are developed to reduce inflammation in arthritis.
T cell: A type of white blood cell known as lymphocytes; they play a central role in immunity.
T helper cell: A subset of T cells that act as the “middlemen” in the immune system. Once activated, they divide rapidly and secrete cytokines, which regulate or “help” the immune response.
Fibroblast: A type of cell that provides a structural framework for many tissues; they are the most common cells of connective tissue in animals.
Macrophage: A type of cell within the tissues that originate from specific white blood cells called monocytes. Their role is to phagocytose (engulf and then digest) cellular debris and pathogens and to stimulate immune cells to respond to the pathogen.
Chang SH, Dong C. A novel heterodimeric cytokine consisting of IL-17 and IL-17F regulates inflammatory responses. Cell Res 2007;17:435-40. DOI:10.1038/cr.2007.35