Immune cells are generally described as soldiers fighting viruses and bacteria invade. But they can also lead to another battle: the war against fat. When mice lacking a specific type of immune cells, the researchers discovered, they become obese and showed signs of high blood pressure, high cholesterol and diabetes. The results have yet to be replicated in humans, but they are already helping scientists understand the triggers metabolic syndrome, a set of conditions associated with obesity.
The new study "definitely moves the field forward," says immunologist Vishwa Deep Dixit of the Yale School of Medicine, who was not involved in the work. "The data seems really solid."
scientists already know that there is a correlation between inflammation and an immune response and increased obesity. But because the fat cells themselves can produce inflammatory molecules, distinguish whether the inflammation causes weight gain or is just a side effect has been difficult.
When he fell on this new cellular link between obesity and the immune system, immunologist Yair Reisner of the Weizmann Institute of science in Rehovot, Israel, studying something completely different: autoimmune diseases an immune molecule called perforin had already been shown to kill diseased cells by drilling a hole in their outer membrane.. Reisner's group suspected that dendritic cells containing perforin could also destroy the body's own cells in certain autoimmune diseases. To test the idea, Reisner and colleagues developed mice lacking dendritic cells perforin waving, then waited to see if they have developed autoimmune diseases.
"We were looking for classical autoimmune diseases," says Reisner. "Quite surprisingly, we found that the mice gained weight and developing metabolic syndrome."
mice lacking dendritic cells with perforin had high levels of cholesterol, insulin resistance early signs and molecular markers in the blood associated with heart disease and high blood pressure. and a look at the immune system mice revealed that they also had a different balance of T-type white blood cells that directs immune-than-normal responses, Reisner and colleagues report online today in Immunity . When researchers removed these mouse T cells, however, the lack of more triggered dendritic cells obese become animals or of developing metabolic syndrome.
the results, Reisner said, suggests that the normal role perforin-positive dendritic cells is to keep certain populations of T cells under control. Just acts as perforin to kill cells infected with the virus, it can be directed to kill subsets of T cells unnecessary, he thinks. When the brakes are taken from these T cells, they cause inflammation in fat cells, which leads to an altered metabolism and weight gain.
"We are now working in human cells to see if something similar happens there," Reisner said. "I think this is the beginning of a new focus on a new regulatory cell. "If the results hold in humans, he said, it could point to a way to use the immune system to treat obesity and metabolic diseases.
Daniel Winer, a endocrine pathologist at the University of Toronto in Canada and lead author of diabetes in January paper linking perforin to insulin resistance, said the new findings overlap with the study. his group found that mice lacking perforin throughout their entire immune system, not only in dendritic cells and fed a high fat diet developed the early stages of diabetes. the new document builds on that by focusing on dendritic cells perforin-positive and showing the same link in the absence of a diet high in fat. "It provides further evidence that the immune system plays an important role in the regulation of obesity and insulin resistance."
Even if the results are valid in humans, however, research is still far from lead to treatments for obesity or metabolic disease, said Dixit. "Speaking of the therapeutic at this stage would be a bit exaggerated." After all, perforin injection into the body could kill cells beyond those T cells promoting obesity, he said. In addition, we can not live without T cells at all, they are vital to immunity against the disease. But research on what T cells recognize when they look for fat cells and cause inflammation in adipose tissue may eventually reveal targets drugs.
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