Our immune system is so powerful that it can sometimes attack parts of our body, causing autoimmune disorders. Today, it is well known that there is a regulatory mechanism in the body, called peripheral immune tolerance, which prevents the immune system from going to overboard, but scientists made a long journey before explaining how it works.
The Nobel Prize for Medicine, declared on Monday, honors three scientists who made a leading discovery with that trip. Shimon Shakguchi, currently with the University of Osaka, discovered regulator T cells, the guards that help prevent the immune system from attacking the body. Independently, Mary E Branch (Institute for Systems Biology, Seattle) and Frederick J Ramsdel (Sonoma Biotheraputics, San Francisco) identified a gene, which could be autoimmune disease when mutated. Later, Shakguchi fulfilled Ara by installing that the same gene regulator controls the development of T cells.
Openheimer to Q
For the Nobel Prize winner, the yatra began with the discovery of Shakguchi in the 1980s, and was carried forward by Branco and Ramsdel’s work in the 2000s of the 1990s. But in the 1940s, in the 1940s, seeds were also laid during the Manhattan project led by Robert J Openhaimer.
Researchers who develop atomic bombs were studying the results of radiation on mice. They found that some male mice were born with scals skin, a extremely increased spleen and lymph glands; They lived for a few weeks.
Since only male rats are affected, it was clear that the X chromosome should be diseased. A female has two X chromosomes, so if one is defective, a healthy person compensates for it, but he can pass on to mutate for men in future generations.
Five decades later, Branco and Ramsdel examined the mouse strain, named “Long”. Then working in Washington -based biotech company, Cellitech Chiosines, he estimated that square rats could provide clues to pharmaceuticals for autoimmune diseases.
Investigations revealed that the organs of the mice were being attacked by T cells – doing something that made the immune system evil. Branco and Ramsdel discovered the mutant genes, in those days a laborious task was not available. It took him several years before identifying the defective gene, which he named FoxP 3.
It was implications for human health. A rare autoimmune disease that affects boys, called IPEX, is also connected to the X chromosome. By mapping the gene samples, the researchers established that the IPEX is a human counterpart of the rats’ square disease; Mutation in the same foxp3 gene causes both diseases.
All this lies that the FoxP3 can be important in the work of the gene regulator T cells, which was previously discovered by Sakaguchi. Two years later, it was re -established that established that it was actually the case.
Finding system
Prior to the establishment of the concept of regulator T cells, scientists proposed a population of cells called “suppressor” T cells, suggesting that over-the-top immunity was prevented. But this idea changed in the last 30 years, Srini V. Kaveri, Research of Research (Emeritus), Center de Rechreche Des Cordelliers (CNRS), Paris.
“The accurate mechanism of accounting for these oppressive effects was not clearly defined at the molecular and bio -chemical level. This was because the actual cells that carried the mitigation function were not separated with specific markers. Also, as the findings could not be re -introduced, the area was not reinforced, the area was not faded, and the oppressed cells were convinced.”
However, it was known that the organ key for T cell development is thymus (so T) in the upper chest. This would mean that T cell activity should be stopped by removing the thymus. In the 1980s, Sakaguchi colleagues found some opposite: When they removed the thymus from three days old mice, the immune system went to overdrive and mice developed autoimmune disease.
Subsequently, Sakguchi separated T cells from healthy mice and injected them into mice without a thymus. This time, T cells appeared that can protect mice from autoimmune diseases. Driver – Before identifying regulator T cells, they were characterized by a decade, which is characterized by protein CD4 and CD25.
Decades later, Sakaguchi added more information in the work he started. Branco and Ramsdel, after identifying the FoxP3 genes, Sakaguchi and other researchers proved that this gene regulator controls the growth of T cells. These cells not only prevent other T cells from attacking the body, but also ensure that the immune system cools down after eliminating an invader.
why it matters
Today, a lot is understood how T cells work, affect the development of new remedies.
“Tregs prevent the growth and multiplication of harmful cells and can also prevent malignant cytokine production by pathogenic T cells. In addition to harmful T cells, Tregs can target many other cell types, including antigen presenting cells Can, ”Kaveri said.
Sometimes, regulatory T cells can be a barrier. Tumors can attract a large number of regulatory T cells that mold them from the immune system. Researchers are trying to find ways to eliminate this wall so that the immune system can reach the tumor.
On the other hand, in autoimmune diseases, researchers are trying to find ways to promote the formation of regulator T cells. Researchers are also trying to separate regulatory T cells from a patient, multiplying them into a laboratory and returning them to the patient, thus giving them more regulatory T cells.
“Terrible autoimmune disease cortison can now be dealt with in a specific way. In our laboratory in Paris, we have described an approach by which we can expand the tregs in patients with autoimmune and inflammatory diseases,” Kaveri said.
“Treatment of many diseases is particularly dependent on transplantation that were large challenges, now within reach … It is all possible for a better understanding of the mechanism of peripheral tolerance. Although TREGS is not the only actor of peripheral tolerance, at this time, they somehow capture,” he said.
