Navigation Links
Suspected cause of type 1 diabetes caught 'red-handed' for the first time
Date:5/9/2008

May 8, 2008 -- Scientists at Washington University School of Medicine in St. Louis working with diabetic mice have examined in unprecedented detail the immune cells long thought to be responsible for type 1 diabetes.

Researchers were able to examine the immune cells from isolated insulin-making structures in the pancreas known as the islets of Langerhans. They caught the immune cells, known as dendritic cells, "red-handed": carrying insulin and fragments of insulin-producing cells known as beta cells. This can be the first step toward starting a misdirected immune system attack that destroys the beta cells, preventing the body from making insulin and causing type 1 diabetes.

The results, reported online in The Proceedings of the National Academy of Sciences, push scientists a step closer to finding ways to treat this condition.

"Now that we've isolated dendritic cells from the pancreas, we can look at why they get into the pancreas and determine which of the materials that they pick up are most critical to causing this form of diabetes," says senior author Emil R. Unanue, M.D., the Paul and Ellen Lacy Professor of Pathology. "That may allow us to find ways to inhibit dendritic cell function in order to block the disorder."

The American Diabetes Association estimates that 1 million to 2 million Americans suffer from type 1 diabetes, which is also called juvenile diabetes because it frequently develops in children.

Patients require insulin injections to survive because the immune system has destroyed the islets of Langerhans, which contain the body's only beta cells. The insulin these cells make is required for the critical task of regulating blood sugar levels.

Scientists detected dendritic cells in the islets years ago. Dendritic and other antigen-presenting cells are the sentinels of the immune system: They pick up bits of protein from around the body and present them to lymphocytes to initiate an immune system reaction. The lymphocytes lead immune attacks against foreign invaders like bacteria and viruses and eliminate them, clearing infections. But when interaction between an antigen-presenting cell and a lymphocyte leads to a part of the body being mistakenly identified as alien, the resulting attack harms the body, causing autoimmune diseases.

Although dendritic cells' presence in the islets and their ability to summon immune attacks made them likely suspects in type 1 diabetes, they were challenging to isolate from the pancreas for closer examination.

"They're very tiny and there are only about 5 to 10 of them per islet, each of which contains approximately a thousand cells," explains Unanue. "So the senior postdoctoral researcher in the lab who did this work, Boris Calderon, had to develop some sophisticated cellular assays to pick them up."

Calderon, M.D., found indications that the cells were carrying granules of insulin and pieces of proteins from beta cells on their cell surfaces. To test whether this cargo carried by the dendritic cells had the potential to trigger an immune attack on beta cells, Calderon exposed the dendritic cells to lymphocytes taken from diabetic mice. The lymphocytes were activated by the dendritic cells of the islets and switched into attack mode.

In a separate line of research, Unanue's lab has learned that dendritic cells in the pancreas may normally have beneficial effects on the health of beta cells. They've shown that when dendritic cells are absent from the pancreas, the beta cells are smaller, an indication that they're not as healthy.

"We think these dendritic cells aren't in the pancreas by accident," says Unanue. "We believe that in the normal individual they help maintain the health of beta cells. But in a person with autoimmune diabetes, they appear to start the problems that destroy beta cells."

The key distinction likely lies in a group of proteins called the major histocompatibility complex (MHC). Two decades ago, Unanue and Paul Allen, Ph.D., the Robert L. Kroc Professor of Pathology and Immunology, showed that the MHC provides the stage on which antigen-presenting cells show bits of protein or peptides to other immune system cells. Scientists believe autoimmune conditions like type 1 diabetes are caused by differences in what the MHC binds to and how it presents that material to immune attack cells. In support of this theory, Unanue's laboratory and that of Michael Gross, Ph.D., Washington University professor of chemistry, have collaboratively shown that the genes that encode the MHC proteins in the diabetic mouse are unique and bind to a set of very characteristic peptides.

In addition to studying what protein fragments carried by dendritic cells are essential for causing type 1 diabetes, Unanue and others are working to learn how genetic variations in the MHC alter the chances that the immune system will mistakenly attack the body.


'/>"/>

Contact: Michael Purdy
purdym@wustl.edu
314-286-0122
Washington University School of Medicine
Source:Eurekalert

Related medicine news :

1. Unsuspected protein determines resistance to breast cancer treatment
2. Soaking Potatoes Before Frying Cuts Suspected Carcinogen
3. Ultrasound first, not CT, for diagnosing suspected acute appendicitis
4. Drug for cluster headaches may cause heart problems
5. Study Points to Cause of Vioxx Heart Risk
6. Damp, Moldy Homes May Cause Depression
7. Constipations Many Causes and Cures
8. High Co-Pays Cause Seniors to Go Without Meds
9. 13 percent of women stop taking breast cancer drug because of side effects, U-M study finds
10. Vocal cord dysfunction may be caused by work
11. Study finds drug spending caps cause some seniors to quit taking key medicines
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/4/2016)... ... 04, 2016 , ... With the stamp of approval from the United States ... National Cancer Research Month. According to the American Cancer Society (2016) , this ... one in four Americans dying as a result. , With numbers as influential as ...
(Date:5/4/2016)... ... May 04, 2016 , ... Vasont ... Vasont Universal Integrator (VUI) extension supports the latest release of Adobe FrameMaker, Release ... 2015 interlace the process of creating, editing and storing XML. , ...
(Date:5/3/2016)... ... , ... ProIntro Glitch is a set of 30 self-animating glitch-themed intros created ... to add a terrifying opener to any video or media. Choose from unique styles ... greater contrast, all the user has to do is increase the turn on background ...
(Date:5/3/2016)... ... May 03, 2016 , ... Healing Cancer in This Century is ... move toward recovery and is offered by creator and visionary Carlos Caridad. Healing ... Radio show considering medical and healing modalities of the fields of Integrative, Alternative, ...
(Date:5/3/2016)... ... ... is now open for the 31st annual AIDS Walk Boston & 5K Run , ... Esplanade. The event regularly draws thousands of participants, making it AIDS Action Committee’s largest annual ... by the USA Track & Field Association. , The AIDS Walk & 5K Run ...
Breaking Medicine News(10 mins):
(Date:5/3/2016)... , May 3, 2016  Specialty Silicone Fabricators ... that shows how a cleanroom works. The free ... about science and technology. ... a technology company, SSF enthusiastically supports the Science, ... educators foster the next generation of innovators. We ...
(Date:5/3/2016)... , May 3, 2016 ... bekannt, dass sie einen entscheidenden Meilenstein durch ... Ein Aufruf zum Handeln, um Patientenresultate  bei ... trägt zu Fortschritten im Verständnis der Hepatischen ... ein Bewusstsein für Hepatische Enzephalopathie in der ...
(Date:5/2/2016)... Mass. , May 2, 2016  While nearly ... that osteoporosis can have on their health, only about ...   according to the results of a new survey ... To mark the start of National Osteoporosis Month, Hologic ... health, which affects nearly 56 million Americans. ...
Breaking Medicine Technology: