Navigation Links
Regulatory immune cell diversity tempers autoimmunity in rheumatoid arthritis
Date:5/8/2012

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 inflammationresulting in pain and swellingaround 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" moleculesa 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."


'/>"/>

Contact: Greg Lester
glester@wistar.org
215-898-3943
The Wistar Institute
Source:Eurekalert

Related medicine news :

1. Regulatory enzyme overexpression may protect against neurodegeneration in Huntingtons disease
2. Moffitt Cancer Center researchers find regulatory T-cell clue to help prevent GVHD
3. FDA awards Georgetown University a Center of Excellence in Regulatory Science & Innovation
4. Key regulatory genes often amplified in aggressive childhood tumor of the brainstem
5. FDA should invest in developing a new regulatory framework to replace flawed 510(k) medical device clearance process
6. Specialized regulatory T cell stifles antibody production centers
7. Newly discovered regulatory mechanism essential for embryo development and may contribute to cancer
8. “Global Supply Chain Visibility and Security; Business Necessity, Regulatory Imperative”
9. RAPS Seeks Nominations for Regulatory Awards, RAPS Fellows
10. iSirona Appoints Chief Quality and Regulatory Officer to Oversee Quality Initiatives
11. NIH-FDA Joint Briefing on Regulatory Science Collaboration
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/13/2016)... ... , ... The producers of Enterprises TV are pleased to present ... world of instantaneous consumption proves very convenient for businesses. With new technologies constantly becoming ... which pollutes our air, water, and soil. It can also threaten the lives of ...
(Date:2/13/2016)... ... 13, 2016 , ... DDi , a Makro company, ... for its expertise in eClinical Solutions. DDi has built its solution competency with ... of global clients. DDi provides smarter technology for Clinical Development, Regulatory and Enterprise ...
(Date:2/12/2016)... ... February 12, 2016 , ... ... to funding innovative lymphoma research and serving the lymphoma community through a comprehensive ... members of South Florida’s philanthropic community at its 10th anniversary Fashion Luncheon on ...
(Date:2/12/2016)... ... February 12, 2016 , ... Coco Libre, the maker ... Red Carpet Events LA GRAMMY’s Style Lounge Event. Coco Libre will offer musicians and ... hydrated before the big event. The invitation-only gifting suite, held this year at the ...
(Date:2/12/2016)... (PRWEB) , ... February 12, 2016 , ... Fisher House ... Vegas Mayor John J. Lee, Nevada Military Support Alliance president Scott Bensing, and Peggy ... at the VA Southern Nevada Healthcare System. This will be the first Fisher ...
Breaking Medicine News(10 mins):
(Date:2/12/2016)... Feb. 12, 2016   National Community Pharmacists Association ... MBA issued the following statement today in response to ... the Centers for Medicare & Medicaid Services (CMS) ... beneficiary advocates and others: patient advocacy organizations ... still reviewing the full CMS analysis. Our initial reaction ...
(Date:2/12/2016)... , Feb. 12, 2016  Diplomat Pharmacy, Inc. (NYSE: DPLO ) is pleased to ... Account Management and Payor Strategies effective Jan. 23, 2016. ... ... ... Diplomat Specialty Pharmacy ...
(Date:2/12/2016)... MONTREAL , February 12, 2016 ... sofern nicht anders vermerkt)   ... Unternehmens http://www.telestatherapeutics.com abrufbar.    ... Website des Unternehmens http://www.telestatherapeutics.com ... Inc. (TSX:TST; PNK:BNHLF) veröffentlichte heute seinen Konzernabschluss ...
Breaking Medicine Technology: