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Distinct set of white blood cells found to set the pace of wound repair

Submitted by on 26 September, 2018 – 4:32 pm
After more than 50 experiments on mice, scientists at Johns Hopkins doctors have traced the basic measures taken by a particular set of white blood cells in determining the pace of recovery from severe lung injury.

White blood cells called regulatory T cells or regulatory T cells for short, and his best-known function is to maintain the body’s immune system attacks its own healthy tissues.

“Our study results are the first and leading critics in the search for treatments for a medical condition that until now had none, despite its high mortality,” says lead study investigator and pulmonologist Landon King, MD “When a patient presents with acute lung injury, we want the team to critical care medicine could do more to stabilize the patient on a respirator, “says King, director of critical care medicine and pulmonary medicine at Johns Hopkins University School of Medicine.

King says the study opens the door to a new field in research and development of drugs that either speed up the subsequent activation of regulatory T cell injury, or supplement the regulatory T cell levels in people who can be relatively deficient in lymphocytes of any of lung diseases or chemotherapy. Lymphocyte is the technical term for a type of white blood cell.

About 200,000 Americans have some form of sudden, acute lung injury (ALI) annually, in which the inflammation has spread through both lungs, making breathing difficult and the body starved of much needed oxygen. These include people with acute respiratory distress syndrome caused by severe infection, the most severe form of ALI. Also included burn victims, people with chest injuries from car accidents, and cancer patients who have had adverse reactions to platelet transfusion of donated blood. Almost all people with ALI requiring mechanical ventilation by the fans, and nearly 75,000 die annually.

The team of experts from Johns Hopkins, lung, the results of the joint study to be published in the Journal of Clinical Investigation online September 21, said his three-year investigation is believed to be the first to distinguish immune system function in wound repair in lung function immediately after injury and inflammation that follows. They add that the study is also the first laboratory and clinical analysis to show how the body is built-in system of natural regulatory T cells can be accelerated or slowed down, either help or hinder the healing of severely damaged lung tissue.

Encouraged by the lack of treatment options, the King and his team began to track and trace the biological steps involved in the recovery of Ali with an experiment on mice that were already serving as a laboratory model for lung injury. As part of the laboratory model, mice inhaling a bacterial substance known to seriously damage both lungs within 24 hours, with inflammation, on average, reaching a maximum after four days. In mice that survive, the average recovery time is 10 days.

Researchers had long assumed that an initial increase in levels of blood cells deep within the cavities of the lung tissue that occurs in mice and humans, was the first response of the immune system to inflammation of lesions. But the Hopkins scientists were surprised to find a higher mortality rate in mice that had been genetically modified to be deficient in lymphocytes, at 40 percent, while the mortality rate in mice with lymphocytes was only 10 per percent.

After determining that the mice lymphocytes were key to recovering from a lung injury, the team prepared to resolve the various roles, if any, played by specific lymphocytes, by injecting mice injured with different types and combinations of cells white blood, such as CD4 and CD8. Only transfusion of spleen cells rich in type CD4 T cells restored the recovery time to normal.

Other experiments conducted by Johns Hopkins pulmonologist Franco D’Alessio, MD, showed that blood levels of a subset of CD4 T cells, technically known as CD4 + CD25 + Foxp3 + regulatory T cells or a proportional jump in the lung spaces from the first day of the injury before a peak on day seven and remained high throughout the recovery on day 10.

This was D’Alessio and his colleagues that the rise was not just a response to injury, but also part of the immediate and natural lung wound repair. When researchers removed T regulatory cells in the damaged lungs of mice, leaving behind all other lymphocytes, the resolution of lung was again halved.

“T cells and the active body’s immune system plays a crucial role in recovery from acute lung injury,” says D’Alessio, a trainer based at Johns Hopkins Bayview Medical Center, “is by no means a passive process, as was thought. ”

To test the potential of regulatory T cells as a potential therapy, the science team doubled bacterial toxin exposures, increased mortality rates of 50 percent in untreated mice. However, mice injected with one million doses of regulatory T cells within one hour of exposure was only 10 percent mortality rate, with many showing signs of rapid recovery after only six days. Similar dose of regulatory T cells provided days after exposure also showed lowered death rates in mice with ALI.

Additional laboratory tests showed that lung tissue levels of other immune system cells involved in inflammation, particularly neutrophils and macrophages, also fell in response to the influx of regulatory T cells, which proves even more regulatory T cells to monitor the change in lung tissue, “in an environment of inflammation of a recovery.”

“Our study should spark lung experts here and in others to change their research focus from near-universal interest in the development of acute lung injury new mechanisms underlying the resolution of lung injury,” says King, associate professor of Johns Hopkins, where he also has the David Marine Professor of Medicine.

Initial results from pulmonary tissue extracts of two persons with an Ali, also reported in the latest survey showed that 48 hours after injury, levels were 10 times normal Treg.

King says his team’s next steps are to identify the process by which Tregs organize the transition of the immune response of mice from injury to repair, isolate and analyze regulatory T cells in the total recovery period in the lungs, with the aim of identifying new drug targets to accelerate biological recovery. He says the experiments elsewhere are already using regulatory T cells to treat people with leukemia to prevent rejection of bone marrow transplants.

Source: Johns Hopkins Medical Institutions

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