Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Autoimmune Disease Strategy Emerges from Immune Cell Discovery

Published: Wednesday, September 11, 2013
Last Updated: Wednesday, September 11, 2013
Bookmark and Share
UCSF experiments halt pancreas destruction in mouse model of diabetes.

Scientists from UC San Francisco have identified a new way to manipulate the immune system that may keep it from attacking the body’s own molecules in autoimmune diseases such as type 1 diabetes, rheumatoid arthritis and multiple sclerosis.

The researchers, led by immunologist Mark Anderson, MD, PhD, a professor with the UCSF Diabetes Center, have discovered a distinctive type of immune cell called an eTAC, which puts a damper on immune responses.

Anderson’s research team found that eTACs reside in lymph nodes and spleen in both humans and mice, and determined that they could be manipulated to stop the destruction of the pancreas in a mouse model of diabetes. The study appears in the September issue of the journal Immunity.

Using green fluorescent protein (GFP) to highlight a key regulatory protein called AIRE, Anderson’s research team tracked down the rare eTACs and their role in a phenomenon known as peripheral tolerance, which helps prevent autoimmune disease throughout the body.

Using eTACs to Turn Off Overactive Immune Cells

The newly described immune cells are of a type known as dendritic cells, which make up less than 3 percent of the cells in the immune system. eTAC cells account for a small fraction of all dendritic cells, Anderson said.

Dendritic cells already have been the focus of new cell therapies to treat cancer. These therapies, which include treatments evaluated in clinical trials at UCSF, have been used to prod dendritic cells to rev up a complementary class of immune cells, called T cells. Treatment causes the T cells to target cancer cells, which, despite being abnormal, would not otherwise be subjected to vigorous attack in the same way as foreign microbial invaders.

However, eTAC cells have the opposite effect. Instead of priming T cells to do battle, eTACs counteract the overactive immune response in autoimmune diseases. Anderson’s team took advantage of this property to demonstrate that eTACs could prevent autoimmune diabetes in mice.

By displaying “self” molecules to T cells that target them, and turning off these T cells for good, eTACs help the immune system tolerate the molecules naturally present within us, Anderson said.

“The mouse model we are working with involves using T cells that normally attack the islet cells of the pancreas, specifically by recognizing a molecule called chromagranin A that is present on islet cells,” Anderson said. “But if the eTACs can get to the T cells first and display chromagranin A, they can prevent T cells from attacking the islets.

Anderson aims to exploit eTACs therapeutically by finding out how to grow them in large numbers outside the body. “We need to figure out how to grow a lot of these cells, to load them up with whatever molecule it is that we want to induce tolerance to, and then to load them back into a patient,” he said. “Such a strategy could help selectively shut down an unwanted immune response, such as the anti-islet immune response in type 1 diabetes.”

eTACs in Bone Marrow Stem Cells

Dendritic cells work with T cells a bit like a sheriff working with a bloodhound. Dendritic cells present not an article of clothing, but rather a specific molecule. If the molecule displayed by the dendritic cell matches the one the T cell was born to target, then that T cell would be activated to expand its numbers and to attack cells or tissues where the molecule is present.

When the interaction is between eTACs and T cells, however, the targeted T cell instead is turned off forever, and never seeks its molecular prey, Anderson said.

The first signal required for activation of a T cell is the display and recognition of the targeted molecule. But a second signal also is required, and eTACs are unable to deliver it, Anderson and colleagues discovered. They lack the molecular arms — molecules called B7-1 and B7-2 — needed to hand off the activating message, which are present on other dendritic cells.

The eTACs arise in the bone marrow from adult stem cells that generate the entire blood system, including immune cells, Anderson said. Compared to using pluripotent stem cells of nearly unlimited potential, it should be easier to figure out how to guide the development of eTACs from bone marrow stem cells, he said.

Anderson’s search for an immune cell that turns off T cells began with the AIRE protein. Anderson helped discover its function more than a decade ago for specialized cells in the thymus. In the thymus, AIRE plays a key role in central tolerance, the phenomenon whereby immune cells in thymus learn to tolerate the body’s naturally occurring molecules shortly after birth. Peripheral tolerance complements central tolerance, and its failure often is responsible for autoimmune diseases that arise long after birth.

Many UCSF faculty members are experts on immune tolerance and autoimmune disease. Another strategy for manipulating the immune system to fight autoimmune disease, pioneered by Jeffrey Bluestone, PhD, the A.W. and Mary Clausen Distinguished Professor of Medicine, Pathology, Microbiology & Immunology at UCSF, already has led to a new treatment being evaluated in a clinical trial for type 1 diabetes. The treatment is based on a type of T cell called the regulatory T cell, which plays a natural role in ending immune responses when infection ends.


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,400+ scientific posters on ePosters
  • More Than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Scientists Create CRISPR/Cas9 Knock-In Mutations in Human T Cells
In a project spearheaded by investigators at UC San Francisco, scientists have devised a new strategy to precisely modify human T cells using the genome-editing system known as CRISPR/Cas9.
Tuesday, July 28, 2015
Simple Technology Makes CRISPR Gene Editing Cheaper
University of California, Berkeley, researchers have discovered a much cheaper and easier way to target a hot new gene editing tool, CRISPR-Cas9, to cut or label DNA.
Friday, July 24, 2015
Printed "Smart Cap" Detects Spoiled Food
It might not be long before consumers can just hit “print” to create an electronic circuit or wireless sensor in the comfort of their homes.
Tuesday, July 21, 2015
Growing Spinal Disc Tissue
Scientists develop new method for growing spinal disc tissue in the lab for combating chronic back pain.
Friday, July 03, 2015
Delivering Drugs to the Right Place
Thomas Weimbs has developed a targeted drug delivery method that could potentially slow the progression of polycystic kidney disease.
Monday, June 29, 2015
The Deep Carbon Cycle
Over billions of years, the total carbon content of the outer part of the Earth—in its upper mantle, crust, oceans and atmospheres—has gradually increased, scientists report.
Tuesday, June 23, 2015
Designing New Pain Relief Drugs
Researchers have identified the molecular interactions that allow capsaicin to activate the body’s primary receptor for sensing heat and pain, paving the way for the design of more selective and effective drugs to relieve pain.
Thursday, June 11, 2015
Engineers Crack DNA Code of Autoimmune Disorders
Researchers have identified an unexpectedly general set of rules that determine which molecules can cause the immune system to become vulnerable to the autoimmune disorders lupus and psoriasis.
Wednesday, June 10, 2015
Genetic Markers for Detecting and Treating Ovarian Cancer
Custom bioinformatics algorithm identifies human mRNAs that distinguish ovarian cancer cells from normal cells and provide new therapeutic targets
Wednesday, May 27, 2015
Researchers Reverse Bacterial Resistance to Antibiotics
Evidence continues to surface that supports the premise that antibiotics which have been out of use could still be effective in treating drug-resistant bacteria.
Friday, May 08, 2015
Industry-Sponsored Academic Inventions Spur Increased Innovation
Analysis questions assumption that corporate support skews science toward inventions that are less useful than those funded by the government or non-profit organizations.
Monday, March 24, 2014
May the Cellular Force be With You
Like tiny construction workers, cells sculpt embryonic tissues and organs in 3D space.
Friday, December 13, 2013
Grant Supports Creation of Patient-Derived Stem Cell Lines
Researchers have received a two-year, $600,000 grant from the National Institute on Aging to develop and study patient-derived stem cell lines.
Thursday, December 12, 2013
Prostate Cancer Stem Cells are a Moving Target
Researchers have discovered how prostate cancer stem cells evolve as the disease progresses, a finding that could help point the way to more highly targeted therapies.
Friday, December 06, 2013
International Fruit Pest Targeted by Genomic Research
The spotted wing drosophila is itself being targeted, thanks to groundbreaking genome sequencing.
Friday, December 06, 2013
Scientific News
RNAi Screening Trends
Understand current trends and learn which application areas are expected to gain in popularity over the next few years.
Diagnostic Test Developed for Enterovirus D68
researchers at Washington University School of Medicine in St. Louis have developed a diagnostic test to quickly detect enterovirus D68 (EV-D68), a respiratory virus that caused unusually severe illness in children last year.
How a Kernel Got Naked and Corn Became King
Ten thousand years ago, a golden grain got naked, brought people together and grew to become one of the top agricultural commodities on the planet.
Sweet Revenge Against Superbugs
A special type of synthetic sugar could be the latest weapon in the fight against superbugs.
New Material Opens Possibilities for Super-Long-Acting Pills
A pH-responsive polymer gel could create swallow able devices, including capsules for ultra-long drug delivery.
How To Keep Your Rice Arsenic-Free
Researchers at Queen’s University Belfast have made a breakthrough in discovering how to lower worrying levels of arsenic in rice that is eaten all over the world.
New Tool For Investigating RNA Gone Awry
A new technology – called “Sticky-flares” – developed by nanomedicine experts at Northwestern University offers the first real-time method to track and observe the dynamics of RNA distribution as it is transported inside living cells.
Computer Model Could Explain how Simple Molecules Took First Step Toward Life
Two Brookhaven researchers developed theoretical model to explain the origins of self-replicating molecules.
New Tech Enables Epigenomic Analysis with a Mere 100 Cells
A new technology that will dramatically enhance investigations of epigenomes, the machinery that turns on and off genes and a very prominent field of study in diseases such as stem cell differentiation, inflammation and cancer has been developed by researchers at Virginia Tech.
Access Denied: Leukemia Thwarted by Cutting Off Link to Environmental Support
A new study reveals a protein’s critical – and previously unknown -- role in the development and progression of acute myeloid leukemia (AML), a fast-growing and extremely difficult-to-treat blood cancer.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!