News: New Immune Cell Found to Be a Key to Inflammatory Diseases

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New Immune Cell Found to Be a Key to Inflammatory Diseases

Newswise — 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. 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

(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.

" 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. researchers collaborated with

scientists from the University of Washington, the Institute for

Systems Biology in Seattle and s 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.

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 says.

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, " says 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 asthmalike symptoms.

Dong says the researchers hypothesize 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, he says.

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 says. " 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. "

The study was funded by grants from the National Institutes of

Health, the Arthritis Foundation, the Cancer Research Institute and

M. D. Cancer Center.

http://www.newswise.com/p/articles/view/515022/