Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Natural method for clearing cellular debris provides new targets for lupus treatment

24.02.2012
Cells that die naturally generate a lot of internal debris that can trigger the immune system to attack the body, leading to diseases such as lupus.
Now Georgia Health Sciences University researchers report that an enzyme known to help keep a woman's immune system from attacking a fetus also helps block development of these autoimmune diseases that target healthy tissues, such as DNA or joints.

The findings point toward new treatment strategies for autoimmune diseases, which are on the rise in light of a germ-conscious society that regularly destroys many of the previously pervasive microbes that made the immune system more tolerant.

"The basic premise of lupus is you have lost normal tolerance to yourself, your own proteins and DNA," said Dr. Tracy L. McGaha, GHSU immunologist and corresponding author of the study published in Proceedings of the National Academy of Sciences.

They found that IDO, or indoleomine 2,3-dioxegenase, helps promote tolerance to debris generated by natural cell death and that when IDO is removed from the mix, the debris spurs an immune response that can trigger autoimmune disease. In mice genetically programmed to develop lupus, blocking IDO resulted in earlier, more aggressive disease.

"This connects IDO and macrophages. It's a newly described role for IDO in regulation of tolerance toward self," McGaha said. Consequently, increasing IDO production or its downstream effects might be a way to regain lost tolerance, he said.

They studied activity in the spleen, a hard-working immune organ, that constantly filters blood. In a perfectly orchestrated defense, the entrance to the spleen is surrounded by immune cells that scour blood for viruses, bacteria, even fat and cholesterol floating by.

A nearby subset of macrophages, which are essentially scavengers, then capture and consume the undesirables, McGaha said. Interestingly, a lot of what macrophages consume is dead immune cells.

Macrophages also appear to help keep the peace by preventing the immune system from joining the fray. McGaha earlier found that if he destroyed macrophages, then fed the spleen dead cells, there was inflammation instead of calm. "That tells us there is something inherent in this subset of macrophages that is important for the suppressive process," McGaha said referencing the paper published in 2011 in the journal Blood.

The new paper shows IDO is part of that "something." Efficient elimination of cell debris while keeping nearby immune cells quiet is important because some debris is known to grab the attention of the immune system, McGaha said. He noted that it's normal – and healthy – for damaged cells to become targets.

"We are really interested in this process of normal cell debris removal because in lupus, it's thought to be one of the main drivers of inflammation," he said.

The immune system has points of expansion and regulation where it decides whether or not to act. Knowing key points, such as IDO's regulatory role, provides treatment targets that can interrupt a destructive cascade of immune activity, McGaha said. Previous studies have shown evidence of self-attack is present many years before disease symptoms appear, he said.

Environmental assaults, such as a bad sunburn, can be the initial trigger of the abnormal immune response in diseases like lupus. In healthy individuals, the immune system rises to the occasion of an infection then goes back to baseline. In autoimmune disease, patients tend not to return to normal levels.

GHSU's Drs. Andrew Mellor and David Munn reported in 1998 in the journal Science that the fetus expresses IDO to help avoid rejection by the mother's immune system. Subsequent studies have shown tumors also use it and that it could help transplanted organs escape rejection. They suggested that McGaha look at IDO as a regulatory mechanism used by macrophages.

Toni Baker | EurekAlert!
Further information:
http://www.georgiahealth.edu

Further reports about: DNA Health Sciences IDO autoimmune disease immune cell immune response immune system

More articles from Life Sciences:

nachricht Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>