New way to block inflammation in autoimmune disease

Posting this because some consider CFS/FMS to be autoimmune diseases

U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH NIH News
National Institute of Arthritis and Musculoskeletal and Skin Diseases 
(NIAMS) http://www.niams.nih.gov/
National Institute of Allergy and Infectious Diseases (NIAID)) 
http://www.niaid.nih.gov/
Embargoed For Release: Thursday, June 19, 2008, 12:00 pm EDT

CONTACT: Trish Reynolds, NIAMS, 301-496-8190, e-mail: 
patricia.reynolds@nih.gov

NIAMS SCIENTISTS FIND POTENTIAL NEW WAY TO BLOCK INFLAMMATION IN 
AUTOIMMUNE DISEASE

Researchers from the National Institute of Arthritis and 
Musculoskeletal and Skin Diseases (NIAMS), a part of the National 
Institutes of Health (NIH), have identified a promising new target 
for autoimmune disease treatment -- a cell-surface receptor called 
DR3. Their research in mice, published on line in the journal 
"Immunity," suggests that blocking this receptor could slow or stop 
the damaging inflammation characteristic of autoimmune diseases, 
potentially without leaving the body vulnerable to serious 
infections, as many current therapies do.

DR3 is a protein on the surface of cells. It is a member of the tumor 
necrosis factor (TNF) family of receptors, which bind to molecules 
related to TNF, a cell-signaling protein that promotes inflammation. 
Many of today's most potent treatments for inflammatory diseases, 
such as rheumatoid arthritis and psoriasis, interfere with the action 
of TNF, thereby blocking inflammation. Since current anti-TNF 
therapies don't work in all autoimmune diseases, however, the 
researchers turned to the study of DR3, which is a close relative of 
TNFR1, the main receptor for TNF.

Working with mouse models of asthma and multiple sclerosis, both 
immune system diseases, the researchers found that mice engineered to 
lack DR3 were resistant to those diseases. "The implication is that 
blocking DR3 in mice, and possibly in humans, is a potential therapy 
for these diseases and perhaps others in which the immune system goes 
awry," said Richard Siegel, M.D., Ph.D., a scientist in the NIAMS' 
Immunoregulation Group, who led the research effort.

While closely related to TNFR1, DR3 is expressed in T cells, a 
different kind of immune cell (a white blood cell that identifies and 
fights infection) than those that express TNFR1, Dr. Siegel said. The 
NIAMS group collaborated with a laboratory in Cardiff, Wales, which 
had generated genetically engineered mice deficient in DR3, as well 
as with a research group at the NIH's National Institute of Allergy 
and Infectious Diseases (NIAID), which has developed mouse models of 
disease with strong T cell components, such as asthma and multiple 
sclerosis. "These findings open up new avenues for therapy of these 
two diseases as well as to other autoimmune diseases in which T cells 
play a role in causing or perpetuating the disease," said Siegel.

The researchers hope that DR3-blocking agents will be effective anti-
inflammatory treatments someday. Siegel noted that if they were to be 
used in rheumatic diseases, they would be a complement to strategies 
that block TNF because they hit a different arm of the immune system. 
"It could be potentially synergistic or complementary," he said.

Of critical importance, the NIAMS scientists found that removing DR3 
did not appear to suppress the immune response or the ability to 
fight infection within the mice -- a problem with many other 
treatments for autoimmune disease. "We could see the effect of DR3 
deficiency in the diseased organ, but when we looked systemically at 
the immune response at other places in the mouse, it was barely 
affected," said Dr. Siegel. The group's findings suggest that DR3-
blocking agents might be more effective at specifically treating 
autoimmune disease without breaking down the body's defenses against 
infections, a long-sought goal of researchers in the field.

For more information about the NIAMS' Immunoregulation Group within 
the Autoimmunity Branch of the Intramural Research Program, visit the 
NIAMS Web site at http://www.niams.nih.gov/Research/Ongoing_Research/Branch_Lab/Autoimmunity/irg.asp

For more information about autoimmune diseases, visit the Medline 
Plus Web site, a service of the NIH's National Library of Medicine, 
at http://www.nlm.nih.gov/medlineplus/autoimmunediseases.html

NIAID is a component of the National Institutes of Health. NIAID 
supports basic and applied research to prevent, diagnose and treat 
infectious diseases such as HIV/AIDS and other sexually transmitted 
infections, influenza, tuberculosis, malaria and illness from 
potential agents of bioterrorism. NIAID also supports research on 
basic immunology, transplantation and immune-related disorders, 
including autoimmune diseases, asthma and allergies. News releases, 
fact sheets and other NIAID-related materials are available on the 
NIAID Web site at http://www.niaid.nih.gov.

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 (NIH), 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.


The National Institutes of Health (NIH) -- The Nation's Medical 
Research Agency -- includes 27 Institutes and Centers and is a 
component of the U.S. Department of Health and Human Services. It is 
the primary federal agency for conducting and supporting basic, 
clinical and translational medical research, and it investigates the 
causes, treatments, and cures for both common and rare diseases. For 
more information about NIH and its programs, visit www.nih.gov.
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Meylan F, et al. The TNF-family receptor DR3 is essential for diverse 
T cell-mediated inflammatory diseases. "Immunity" 29, 1-11, July 2008.