Navigation Links
Joslin researchers increase understanding of genetic risk factor for type 1 diabetes
Date:11/28/2012

BOSTON November 28, 2012 As part of their ongoing research on the role of genes in the development of type 1 diabetes, Joslin Diabetes Center scientists, in collaboration with scientists at the University of Wrzburg, have demonstrated how a genetic variant associated with type 1 diabetes and other autoimmune diseases influences susceptibility to autoimmunity. The findings appear in the upcoming issue of Diabetes.

Recent studies of the human genome have identified genetic regions associated with autoimmune diseases such as type 1 diabetes. Joslin scientists in the Section of Immunobiology seek to understand how genes that are most widely associated with various autoimmune diseases contribute to disease risk.

One of these genes is PTPN22, which plays a role in lymphocyte (immune cell) function. A PTPN22 variant (or mutation) has been implicated as a risk factor for type 1 diabetes and several other autoimmune disorders. PTPN22 is involved in the formation of a key protein known as lymphoid tyrosine phosphatase (LYP), which helps control the activity of T and B cells in the immune system. The PTPN22 mutation generates a variation of LYP with a different molecular structure.

Most studies of the PTPN22 disease variant have suggested that this variant is a gain-of-function genetic mutation that enhances LYP activity and lessens the activity of T and B cells, which increases susceptibility to autoimmunity. "When immune cells are less reactive during the maturation phase of their development, the cells can evade mechanisms that help protect against autoimmunity," says study lead author Stephan Kissler, PhD, of the Section of Immunobiology. However, one study which analyzed data from humans and genetically modified mice suggested that the LYP variant associated with type 1 diabetes is a loss-of-function mutation that reduces LYP activity.

To help resolve the conflicting data, Joslin scientists conducted studies with a unique mouse model developed by Dr. Kissler's graduate student and co-author, Peilin Zheng. Using a technology that combines RNA interference, a method to silence gene expresson, with lentiviral transgenesis, a method to genetically modify animals, the scientists can manipulate gene activity in the most widely used mouse model for type 1 diabetes, the nonobese diabetic mouse (NOD). In this study, the researchers were able to easily turn off and on the PTPN22 gene in the NOD mouse. "We are the first to use this approach in the NOD mouse model," says Dr. Kissler. "It provides a very powerful way to study the contribution of PTPN22 to disease."

When PTPN22 was turned off in mice, mimicking a loss-of-function mutation, the researchers observed an increase in regulatory T cells and a decreased risk of autoimmune diabetes. "This is the first study conducted on the diabetic mouse model that supports the LYP gain-of-function hypothesis," says Dr. Kissler. "Our work should help to resolve the controversy."

By providing additional data that suggests the potential therapeutic value of PTPN22 manipulation, the study may further the development of new therapeutic options that inhibit LYP to reduce or prevent autoimmunity. "Our goal is to treat autoimmunity. Inhibiting LYP in patients may increase regulatory immune cells and could confer protection against autoimmunity, but it remains to be tested if our promising findings in this mouse model are reflected in humans," says Dr. Kissler.

The Joslin scientists are following up on this study to deepen understanding of how inhibiting PTPN22 affects T and B cells.


'/>"/>

Contact: Jeffrey Bright
jeffrey.bright@joslin.harvard.edu
617-309-1957
Joslin Diabetes Center
Source:Eurekalert  

Related biology news :

1. Joslin researchers gain new understanding of diabetes and kidney disease
2. Fracking in Michigan: U-M researchers study potential impact on health, environment, economy
3. NREL researchers use imaging technologies to solve puzzle of plant architecture
4. NIH-funded researchers show possible trigger for MS nerve damage
5. Temple-Penn researchers identify calcium accelerator to keep cell power supply going
6. Researchers detail the migrations of the wood wasp Sirex noctilio
7. Researchers identify a simple way to precipitate phosphorus from the wastewater of a pulp mill
8. Researchers decode birch tree genome sequence for the first time
9. Researchers develop guidebook for promoting healthy lifestyles among Hispanic populations
10. Researchers study links between conflict and fisheries in East Africa
11. A class of RNA molecules protects germ cells from damage, Penn vet researchers show
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Joslin researchers increase understanding of genetic risk factor for type 1 diabetes
(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: