Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Regulatory immune cell diversity tempers autoimmunity in rheumatoid arthritis

09.05.2012
Untangling the root cause of rheumatoid arthritis has been a difficult task for immunologists, as decades of research has pointed to multiple culprits in our immune system, with contradictory lines of evidence.
Now, researchers at The Wistar Institute announce that it takes a diverse array of regulatory T cells (a specialized subset of white blood cells) to prevent the immune system from generating the tissue-specific inflammation that is a hallmark of the disease. Regulatory T cell diversity, the researchers say, provides a cumulative protective effect against rheumatoid arthritis. When that diversity is not present, it allows the immune system to attack joints.

The Wistar scientists presented their findings, developed in a mouse model of rheumatoid arthritis, in the May 1 issue of the Journal of Immunology. Defining the immune mechanisms involved in rheumatoid arthritis could point to new therapies for the disease.

“Our results show, surprisingly, that suppressing the immune response against a single target will not shut down the inflammatory response that causes rheumatoid arthritis,” said Andrew J. Caton, Ph.D., senior author and professor in The Wistar Institute Cancer Center’s Tumor Microenvironment and Metastasis program. “Instead, an array of inflammation-stimulating antigens may be involved in causing the disease, since our study shows that an array of regulatory T cells is required to temper the immune system’s attack on joints.”

Rheumatoid arthritis (RA) is an autoimmune disorder that occurs as the immune system attacks the synovium, the membrane that lines all the joints of the body. It is a common disorder that causes uncontrolled inflammation—resulting in pain and swelling—around the joints. It is thought that approximately one percent of the adult population, worldwide, suffers from rheumatoid arthritis. RA has shown to be exacerbated by drinking and smoking, and the disease can lead to an overall increased risk of death.

While the exact cause of RA is unknown, the Caton laboratory and others have shown that a variety of white blood cells called regulatory T cells (or Tregs) are a necessary component to either restrain (or encourage) the immune system’s inflammatory response. Tregs are activated as molecules on their surface membranes called T cell receptors interact with “friendly” or “self” molecules—a way for the immune system to recognize friend from foe. Mismanagement of these Tregs, which normally serve to restrain the immune system from over-reacting to healthy tissue, could then lead to runaway inflammation.

In this study, the researchers sought to examine how T cell receptors affect the ability of Tregs to suppress arthritis in a mouse that had been bred to express a “self” molecule that drives arthritis. They showed that an array of Tregs given to the mice effectively stops arthritis. Unexpectedly, however, Tregs that are specific for the surrogate “self” molecule do not prevent arthritis.

“We find that the Treg responsible for recognition of the disease-initiating self antigen are sufficient for stopping arthritis, but a diverse repertoire of Tregs are very effective,” Caton said. “All of these Tregs, together, influence other components of the immune system which serves to slow down the inflammatory process that causes RA.”

According to Caton, their findings also point to a possible answer of why the immune system targets the membranes that line joints. Tregs influence other types of T cells to produce a substance known as IL-17, and these cells often travel through the body’s lymphatic system where they then drain out into the joints.

“The big unanswered question of RA is ‘why are joints targeted?’” Caton said. “Of all the tissues in the body, of all the places our immune system could attack, this question remains.”

“One idea is that the immune system isn’t deliberately attacking joints in patients with rheumatoid arthritis,” Caton said, “but the joint inflammation is a side effect of the natural tendency of these cells to accumulate in these areas of the body.”

Funding for this project was provided by the National Institutes of Health’s National Institute for Allergy and Infectious Disease and National Cancer Institute, and a grant from Sibley Memorial Hospital.

The lead author of this study is Soyoung Oh, Ph.D., a postdoctoral fellow in the Caton laboratory, and co-authors include Caton laboratory members Malinda Aitken, Donald M. Simons, Ph.D, Alissa Basehoar, Victoria Garcia, and Elizabeth Kropf.

The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the country, Wistar has long held the prestigious Cancer Center designation from the National Cancer Institute. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. The Wistar Institute: Today’s Discoveries – Tomorrow’s Cures.

Greg Lester | EurekAlert!
Further information:
http://www.wistar.org

More articles from Health and Medicine:

nachricht Novel bone imaging approach provides insights into the progression of knee osteoarthritis
15.07.2020 | Society of Nuclear Medicine and Molecular Imaging

nachricht UTMB researchers have discovered a new antiviral mechanism for dengue therapeutics
14.07.2020 | University of Texas Medical Branch at Galveston

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A new path for electron optics in solid-state systems

A novel mechanism for electron optics in two-dimensional solid-state systems opens up a route to engineering quantum-optical phenomena in a variety of materials

Electrons can interfere in the same manner as water, acoustical or light waves do. When exploited in solid-state materials, such effects promise novel...

Im Focus: Electron cryo-microscopy: Using inexpensive technology to produce high-resolution images

Biochemists at Martin Luther University Halle-Wittenberg (MLU) have used a standard electron cryo-microscope to achieve surprisingly good images that are on par with those taken by far more sophisticated equipment. They have succeeded in determining the structure of ferritin almost at the atomic level. Their results were published in the journal "PLOS ONE".

Electron cryo-microscopy has become increasingly important in recent years, especially in shedding light on protein structures. The developers of the new...

Im Focus: The spin state story: Observation of the quantum spin liquid state in novel material

New insight into the spin behavior in an exotic state of matter puts us closer to next-generation spintronic devices

Aside from the deep understanding of the natural world that quantum physics theory offers, scientists worldwide are working tirelessly to bring forth a...

Im Focus: Excitation of robust materials

Kiel physics team observed extremely fast electronic changes in real time in a special material class

In physics, they are currently the subject of intensive research; in electronics, they could enable completely new functions. So-called topological materials...

Im Focus: Electrons in the fast lane

Solar cells based on perovskite compounds could soon make electricity generation from sunlight even more efficient and cheaper. The laboratory efficiency of these perovskite solar cells already exceeds that of the well-known silicon solar cells. An international team led by Stefan Weber from the Max Planck Institute for Polymer Research (MPI-P) in Mainz has found microscopic structures in perovskite crystals that can guide the charge transport in the solar cell. Clever alignment of these "electron highways" could make perovskite solar cells even more powerful.

Solar cells convert sunlight into electricity. During this process, the electrons of the material inside the cell absorb the energy of the light....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Contact Tracing Apps against COVID-19: German National Academy Leopoldina hosts international virtual panel discussion

07.07.2020 | Event News

International conference QuApps shows status quo of quantum technology

02.07.2020 | Event News

Dresden Nexus Conference 2020: Same Time, Virtual Format, Registration Opened

19.05.2020 | Event News

 
Latest News

Tiny bubbles make a quantum leap

15.07.2020 | Physics and Astronomy

Higher-order topology found in 2D crystal

15.07.2020 | Materials Sciences

Russian scientists have discovered a new physical paradox

15.07.2020 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>