Nat Immunol: how neutrophils prevent the immune system from losing control

February 15, 2020 / bioun / -- scientists at the National Center for cardiovascular research (CNIC) in Madrid, Spain, have found a "release" mechanism that can prevent uncontrolled immune system activity The newly discovered immune control system is located in one of the most important cell types in the immune system, neutrophils The findings, published in the journal Nature Immunology, may have a significant impact on understanding and treatment of diseases such as myocardial infarction, stroke and acute inflammation The immune system consists of a variety of cells that are responsible for defending against external and internal threats To do this, lead researcher Andr é s Hidalgo explains, "they patrol all corners of our bodies, looking for and discovering anything unusual or inappropriate, and taking appropriate action, often leading to invasions or irregular cell death When it works properly, the system eliminates not only the myriad and diverse pathogens that constantly attack us, but also the internal 'mistakes' that occur in our own cells - mistakes that can make them malignant cancers "Source: CNIC, however, the immune system is a double-edged sword If immune cells perform their functions too enthusiastically, they may function in the wrong place or at the wrong time, damaging healthy tissues "For this reason, the immune system has to be precisely regulated," Hidalgo said Failed immune regulation is the basis of human diseases, such as cancer, cardiovascular diseases, autoimmune diseases and neurodegenerative diseases Therefore, it is necessary to understand the mechanism of controlling immune response The new study found a new immune control mechanism, which is located in neutrophils, one of the most important cell types in the immune system Neutrophils are the first immune cells to reach the site of infection or inflammation and try to eliminate the root cause of the problem "Neutrophils are the most abundant circulating immune cells and the first responders to threats "However, neutrophils are highly destructive, and if they are activated in the wrong place or at the wrong time, the same mechanisms used to kill invading pathogens will eventually destroy healthy tissue The antibacterial effect of neutrophils is carried out by a "defense armory" composed of proteins stored in particles Once released, it will induce the formation of neutrophil extracellular traps (NETs) However, the toxicity of these structures is particularly dangerous to highly vascular tissues such as the lungs This new study has found an internal cellular mechanism, which changes the protein content of neutrophils in the circulation, leading to the gradual disappearance of toxic substances in the particles, thus reducing the ability to form nets Therefore, this program destroys the main attacking mechanism of neutrophils This mechanism is driven by the receptor CXCR2 and circadian regulatory factors The results show that neutrophils have "an inherent system that can gradually reduce their ability to launch toxic attacks, so with age, neutrophils will disarm themselves before damaging healthy tissues "Depending on the time of day, there are many diseases that cause more or less damage, and this disarmament program helps explain the origin of these clinical differences," the researchers explained First author Jose Maria adrover commented that thanks to the disarming program, "neutrophils self limit their ability to destroy healthy tissue In addition, in collaboration with the Barcelona hospital clinic, we found that this mechanism directly affects the severity of acute lung injury "The authors of the study believe their findings could have a significant impact on health care "Once we understand how the process works naturally, we can try to manipulate it to achieve clinical benefits," said co-author Alejandra aroca "We have done research in this area and achieved promising results in preclinical models of acute myocardial infarction "Reference: Andr é s Hidalgo et al Programmed 'disarming' of the nuclear protocol reduces the magnitude of information, Nature Immunology (2020) Doi: 10.1038/s41590-019-0571-2