Scientists isolate new immune cell for drug target
key role in inflammatory and autoimmune diseases, which raises the
prospect of finding ways to treat these disorders that include
asthma, arthritis, and multiple sclerosis (MS).
The findings suggest that shutting down the activity of these cells might stop chronic inflammatory diseases from developing in the first place.
In addition, the researchers think that while the findings have no immediate relevance to the field of oncology, it is known that cancer can arise from inflammatory processes.
The researchers, from the University of Texas, think that their findings may point to ways to effectively treat these diseases - if not stop them before they start.
However they also said that while such drugs are years away from development and clinical trials, agents that block the disease mechanisms could represent an effective treatment, based on these results.
In the article, which appears in the November issue of Nature Immunology (released online on Oct. 2), 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.
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 recognise 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.
"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," said the study's lead investigator, Chen Dong, 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 added.
Dong was hopeful that in shutting down the activity of these THi cells, chronic inflammatory diseases might be halted from developing in the first place.
Previous studies of this kind had isolated two such different types of effector T helper cells - 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.
Researchers could not understand the origins of such an inflammatory response in body tissues. The only clue they had was that excess IL-17 molecules are found in arthritic joints, in lungs swollen by asthma and in brain cells that lead to nerve degeneration and the onset of MS.
"But we didn't know which T cells were responsible for secreting IL-17," Dong said.
To find out where IL-17 came from, the researchers designed a series of cell culture studies and mouse experiments. In brief, they "educated" T helper cells to become IL-17 producing cells.
They found that IL-17 is triggered by a unique set of signals that now define this new "lineage" of T helper cells.
"They are completely different from TH1 and TH2 effector cells," said Dong.
They then used a mouse model of MS and demonstrated that they could stop development of the disease with an antibody agent that blocked IL-17.
Finally, they developed a transgenic mouse model of asthma and found that, by producing excessive IL-17 in the lung, they were able to produce asthma like symptoms.
Dong said that the researchers hypothesised that these newly discovered THi cells travel to selected body tissues and release IL-17.
This action, in turn, stimulates expression of "chemokines," which results in a rush of inflammatory cells into the tissue. Thus a chronic inflammatory reaction is set up.
"The scientists don't know what initially sets off activation of the newly discovered T helper cell in diseases such as arthritis and asthma," Dong added.
Dong added: "We don't know why these dangerous helper T cells are activated in the patients, but we now know how they function, and that should take us a long way to understanding and treating these and other inflammatory and autoimmune diseases."
