The molecular roots of inflammatory and autoimmune diseases such as asthma, arthritis, and multiple sclerosis (MS) have been discovered by a team of researchers led by The University of Texas M. D. Anderson Cancer Center. They say their findings may point to ways to effectively treat these diseases - if not stop them before they start.
In a lead article in the November issue of Nature Immunology, the scientists report finding a novel type of "T helper" cell they say is the culprit for initiating chronic inflammation and autoimmunity in a variety of body tissues. This newly described T cell - which they call inflammatory TH cells (or THi) - produces interleukin 17 (IL-17), a potent cytokine that researchers have already linked to an immune system gone awry.
"We suspected that IL-17 is a player in autoimmune and inflammatory diseases, but we didn't understand where IL-17 came from before this finding," says the study's lead investigator, Chen Dong, Ph.D., an associate professor in the Department of Immunology.
"Now we have discovered the source of IL-17 and also have solidly demonstrated that these are the crucial cells that regulate tissue inflammation in autoimmune disease and asthma," he says. "These findings suggest that shutting down the activity of these THi cells might stop chronic inflammatory diseases from developing in the first place."
He adds that while such drugs are years away from development and clinical trials, agents that block IL-17 could represent an effective treatment, based on these results.
Dong and four other M. D. Anderson researchers collaborated with scientists from the University of Washington, the Institute for Systems Biology in Seattle and Johns Hopkins School of Medicine.
While the findings have no immediate relevance to the field of oncology, it is known that cancer can arise from inflammatory processes. Further understanding of how the immune system functions, and how it can go awry, is important, Dong says.
T cells are white blood cells that play a variety of roles in the immune system, including the identification of foreign molecules in the body, such as bacteria and viruses, and the activation and deactivation of other immune cells.
T helper cells are specific T cells that have receptors that recognize and bind to fragments (known as antigens) of the invaders that already have been displayed on the surface of other immune system cells. (These T helper cells are also called CD4 T cells since they express CD4 molecules.) Once the antigen has been bound, these T helper cells become activated, and they morph into "effector" cells which then boost an immune response by secreting "cytokine" molecules such as interleukins and interferons.
Before this study, two such different types of effector T helper cells had been known - type I (TH1), linked to the body's response to microbial infection, and type 2 (TH2), which plays a crucial function in production of B cell antibodies and also is associated with development of allergies.
Although TH1 and TH2 are known to produce powerful cytokines - such as interferon-gamma (IFN-g) and allergy-associated interleukin 4 (IL-4), respectively - they are not inflammatory or associated with production of IL-17, which sets off an errant immune response that results in tissue inflammation.