Navigation Links
New insight into mechanisms behind autoimmune diseases suggests a potential therapy
Date:3/18/2012

LA JOLLA, Calif., March 18, 2012 Autoimmune diseases, such as Type I diabetes and rheumatoid arthritis, are caused by an immune system gone haywire, where the body's defense system assaults and destroys healthy tissues. A mutant form of a protein called LYP has been implicated in multiple autoimmune diseases, but the precise molecular pathway involved has been unknown. Now, in a paper published March 18 in Nature Chemical Biology, researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) show how the errant form of LYP can disrupt the immune system. In doing so, they also found a potential new therapy for autoimmune diseasesa chemical compound that appears to inhibit this mutant protein.

T cells and autoimmune disease

In Caucasian populations, a mutated form of LYP (short for lymphoid tyrosine phosphatase) is the third most common single-gene cause of Type 1 diabetes. It ranks second for rheumatoid arthritis.

Researchers have known that LYP and another protein called CSK (C-terminal Src kinase) work cooperatively to keep the immune system's destructive T cells from being activated. Because the uncontrolled activation of T cells is a hallmark of many autoimmune diseases, the proper functioning of LYP with CSK is thought to keep T cells in check.

While the normal form of LYP can bind CSK, the disease-associated mutant LYP cannot. In the new study, Sanford-Burnham researcher Lutz Tautz, Ph.D. led an international group of scientists in showing that normal LYP can disassociate itself from CSK, which paradoxically makes LYP better at dampening the signals that activate T cells. These findings explain why the mutant form of LYP is better at limiting T cell activation than normal LYP.

"It's still a mystery how a protein that impairs T cell signaling causes autoimmunity," said Tautz. "In a simple model of autoimmunity, you would think the opposite."

One possible explanation, Tautz said, is that the mutant LYP weakens the action of regulatory T cells, which control the other type of T cells, the kind that causes autoimmunity.

"If you have regulatory T cells that are not as active because they have inhibited signaling, then they might not be able to do their job properly," Tautz said.

Towards new therapeutics

In their study, the researchers also screened 50,000 drug-like chemical compounds and found 33 that have a specific effect on LYP activity. One compound, called LTV-1, blocked the action of the mutant LYP protein in human T cells. In fact, under physiological conditions, LTV-1 is the most potent LYP inhibitor reported to date.

Tautz said he plans to next develop the LTV-1 compound further, in part by modifying it chemically to make it more effective as a drug. Tests in mice, however, could be problematic because a separate study recently showed that mice with a corresponding LYP mutation don't get sick at all.

Developing new treatments for autoimmune diseases would help millions of people. Overall, autoimmune diseases affect more than 25 million individuals in the United States alone. According to the U.S. Department of Health and Human Services, autoimmune diseases are a leading cause of death and disability.


'/>"/>

Contact: Heather Buschman, Ph.D.
hbuschman@sanfordburnham.org
858-795-5343
Sanford-Burnham Medical Research Institute
Source:Eurekalert  

Related biology news :

1. Research on flavanols and procyanidins provides new insights into how these phytonutrients may positively impact human health
2. New insights into cloud formation
3. Notre Dame researchers are providing insights into elephant behavior and conservation issues
4. Research offers insight to how fructose causes obesity and other illness
5. Prolific plant hunters provide insight in strategy for collecting undiscovered plant species
6. Metadynamics technique offers insight into mineral growth and dissolution
7. Ecologists gain insight into the likely consequences of global warming
8. New insights into how the brain reconstructs the third dimension
9. New insights come from tracing cells that irreversibly scar lungs
10. Huskies lend insight into mercury risk
11. Genomic sequence and comparison of 2 macaques reveal new insights into biomedical research
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
New insight into mechanisms behind autoimmune diseases suggests a potential therapy
(Date:3/28/2017)... , March 28, 2017 The ... Hardware (Camera, Monitors, Servers, Storage Devices), Software (Video Analytics, ... Region - Global Forecast to 2022", published by MarketsandMarkets, ... 2016 and is projected to reach USD 75.64 Billion ... and 2022. The base year considered for the study ...
(Date:3/24/2017)... 24, 2017 The Controller General of Immigration from ... Abdulla Algeen have received the prestigious international IAIR Award for the ... Continue Reading ... ... Controller Abdulla Algeen (small picture on the right) have received the IAIR ...
(Date:3/23/2017)... The report "Gesture Recognition and Touchless Sensing Market by Technology (Touch-based ... to 2022", published by MarketsandMarkets, the market is expected to be worth USD ... 2022. Continue Reading ... ... ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... and LAGUNA HILLS, Calif. , Oct. ... Cancer Research, London (ICR) and University ... SKY92, SkylineDx,s prognostic tool to risk-stratify patients with multiple myeloma ... MUK nine . The University of Leeds ... partly funded by Myeloma UK, and ICR will perform the ...
(Date:10/10/2017)... ... 2017 , ... San Diego-based team building and cooking events company, Lajollacooks4u, has ... The bold new look is part of a transformation to increase awareness, appeal to ... period. , It will also expand its service offering from its signature gourmet cooking ...
(Date:10/10/2017)... 10, 2017 International research firm Parks Associates announced ... at the TMA 2017 Annual Meeting , October 11 in ... residential home security market and how smart safety and security products impact ... Parks Associates: Smart Home ... "The residential security market has ...
(Date:10/9/2017)... DIEGO , Oct. 9, 2017  BioTech ... biological mechanism by which its ProCell stem cell ... critical limb ischemia.  The Company, demonstrated that treatment ... amount of limbs saved as compared to standard ... the molecule HGF resulted in reduction of therapeutic ...
Breaking Biology Technology: