An international research team led by Italian scientists from Policlinico San Martino in Genoa found that patients with severe COVID-19 experience overexpression of a protein called Notch4, which shrinks during the healing process. In experiments in mice, it has been shown that it can trigger a cytokine storm and blow up the “control system” of the immune system. By eliminating it, the deterioration and death of respiratory infections can be prevented.
between complication of Coronavirus disease,by Coronavirus SARS-CoV-2, One of the most dangerous events is the so-called “cytokine storm”, which comes from immune system Virus invasion can cause acute respiratory distress syndrome (ARDS).The response significantly increased Inflammatory protein/mediator Instead of protecting the organism from catalysisinflammation, Exacerbated the patient’s clinical condition. In some experiments on mouse models (ball) Has been shown to eliminate a specific protein-called Gap 4 -High concentration exists in Lung immune cells For patients with severe COVID-19, it is possible to prevent it from getting worse Respiratory tract infection and also death.This protein is considered to be the “engine” of the cytokine storm, so it may represent a kind of Treatment goals To save the lives of COVID-19 and other diseases that caused it.
This research was conducted by the International Immunology Research Group, which was co-led by scientists from the Clinical Immunology and Translational Medicine Department of IRCCS San Martino Polyclinic in Genoa, and scientists from the Immunology Department of Boston Children’s Hospital, USA. They worked with Harvard Colleagues from the CNR-Pozzuoli Institute of Biomolecular Chemistry, Department of Pulmonary and Intensive Care, University of Massachusetts General Hospital, and other research centers such as the Research and Diagnosis Department of Giannina Gaslini Institute in Genoa, Istanbul, Aziz Sankar University Institute of Experimental Medicine. Professor Raffaele de Palma, a professor of internal medicine at the University of Genoa and an immunologist at the Liguria Hospital, coordinated the research of the scientists. They concluded that:expression Notch4 protein in Circulating regulatory T cells (Tregg)-It can regulate the immune response when pathogens invade-is related to the severity and mortality of COVID-19. On the other hand, in recovered patients, the expression of Notch4 tends to decrease.
Simply put, the excess of Notch4 protein destroys the “control system” of the immune response, thereby changing the immune system and opening the door to the cytokine storm. He explained: “The cytochemical storm is a phenomenon found in patients affected by the severe form of COVID-19. This inflammation exacerbates the inflammation characterized by pneumonia, which is caused by a defect in the control system that fails to prevent the immune response. .” in the press release. “In particular, the results of our work show that in Tregs from lung tissue of people with COVID-19, the Notch4 protein is abnormal: the higher the protein content, the more severe the patient’s condition. The scientist added that In the recovered subjects, the protein concentration returned to normal.
In order to better understand the role of Notch4 protein, scientists have conducted some research. experiment Mice, including specimens “humanized” through genetic engineering.Scientists have them Infected Synthetic pathogens are similar to Viruses and RNA WithInfluenza H1N1; By eliminating harmful proteins, they observed the normalization of the immune response and the improvement of rodent health. “In traditional and humanized mice, the absence of Notch4 in Treg cells or treatment with anti-Notch4 antibodies normalizes innate immune disorders and saves the incidence of diseases induced by synthetic viral RNA analogs or H1N1 influenza Mortality”, we areLearning summary.
Professor De Palma pointed out: “This effect is partly due to the ability of the Notch4 protein to inhibit the activity of a second protein called Amfiregulin, and Amfiregulin plays a fundamental role in preventing inflammation and promoting lung tissue repair.” “Mechanically. , Notch4 inhibits the interleukin 18 induction of interleukin 18, which is a cytokine required for tissue repair,” the scientist in the study explained. Based on these results, Professor De Palma believes that Notch4 represents a potential therapeutic target, “not only against the lung inflammation caused by Covid-19, but also against all the viruses that can attack the tissue.” The details of the study”Notch4 signaling restricts regulatory T cell-mediated tissue repair and promotes severe lung inflammation in viral infections“It has been published in the authoritative scientific journal “Immunology”.