Now, a team of scientists from the Whitehead Institute and the Dana-Farber Cancer Institute have identified a key set of genes that lie at the core of autoimmune disease, findings that may help scientists develop new methods for manipulating immune system activity.
"This may shorten the path to new therapies for autoimmune disease," says Whitehead Member and MIT professor of biology Richard Young, senior author on the paper that will appear January 21 online in Nature. "With this new list of genes, we can now look for possible therapies with far greater precision."
The immune system is often described as a kind of military unit, a defense network that guards the body from invaders. Seen in this way, a group of white blood cells called T cells are the frontline soldiers of immune defense, engaging invading pathogens head on.
These T cells are commanded by a second group of cells called regulatory T cells. Regulatory T cells prevent biological "friendly fire" by ensuring that the T cells do not attack the body's own tissues. Failure of the regulatory T cells to control the frontline fighters leads to autoimmune disease.
Scientists previously discovered that regulatory T cells are themselves controlled by a master gene regulator called Foxp3. Master gene regulators bind to specific genes and control their level of activity, which in turn affects the behavior of cells. In fact, when Foxp3 stops functioning, the body can no longer produce working regulatory T cells. When this happens, the frontline T cells damage multiple organs and cause symptoms of type 1 diabetes and Crohn's disease. However, until now, scientists have barely understood how Foxp3 controls regulatory T cells because they knew almost nothing about the actual genes under Foxp3's purview.
Researchers in Richard Young's Whitehead lab, working closely with immunologist Harald von Boehmer of the Dana-Farber Cancer Institute, used a DNA microarray technology developed by Young to scan the entire genome of T cells and locate the genes controlled by Foxp3. There were roughly 30 genes found to be directly controlled by Foxp3 and one, called Ptpn22, showed a particularly strong affinity.
"This relation was striking because Ptpn22 is strongly associated with type 1 diabetes, rheumatoid arthritis, lupus and Graves' disease, but the gene had not been previously linked to regulatory T-cell function," says Alexander Marson, a MD/PhD student in the Young lab and lead author on the paper. "Discovering this correlation was a big moment for us. It verified that we were on the right track for identifying autoimmune related genes."
The researchers still don't know exactly how Foxp3 enables regulatory T cells to prevent autoimmunity. But the list of the genes that Foxp3 targets provides an initial map of the circuitry of these cells, which is important for understanding how they control a healthy immune response.
"Autoimmune diseases take a tremendous toll on human health, but on a strictly molecular level, autoimmunity is a black box," says Young. "When we discover the molecular mechanisms that drive these conditions, we can migrate from treating symptoms to developing treatments for the disease itself."
David Cameron | EurekAlert!
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration
"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
16.01.2017 | Power and Electrical Engineering
16.01.2017 | Information Technology
16.01.2017 | Power and Electrical Engineering