Organ transplantation in the last 60 years of difficulties ushered in important progress! The latest Science finds new immune mechanisms to prevent chronic rejection.

▎ the latest issue of science, a top academic journal edited by the content team of Wuxi, was published by the University of Pittsburgh School of medicine and the Houston Methodist of Cornell University School of medicine A research team led by hospital reported an important discovery in the immune system, which brought new strategies to solve the problem of chronic rejection in organ transplantation.and this problem has been an important failure reason of organ transplantation in the past 60 years.experimental results in mice showed that the survival time of transplanted organs such as kidney and heart was prolonged several times by treating immune cells based on this finding.in the world, organ transplantation has saved countless lives.taking uremia as an example, renal transplantation is the most effective treatment.since the first successful renal transplantation in 1954, nearly one million uremic patients have been born through renal transplantation.after receiving precious organs, patients are faced with an inevitable challenge - rejection, that is, the immune system will attack the transplanted organ tissue.with the development of surgical techniques, the development of tissue matching techniques, and the continuous emergence of new immunosuppressants, the incidence of acute rejection is greatly reduced, and the survival rate of transplanted organs in the short term is steadily improved.Image Source: 123rf unfortunately, due to the presence of chronic rejection, despite taking immunosuppressive drugs and enduring adverse reactions, the transplanted organ or tissue tends to deteriorate gradually in the end.renal transplantation is still an example, and nearly half of the transplanted organs gradually lose function within 10 years."the rate of acute rejection within one year after transplantation has decreased significantly, but many recipients of organ transplantation may need a second transplant for life due to chronic rejection."Fadi g. lakkis, MD, director of the Transplantation Institute at the University of Pittsburgh, said he was one of the co authors of the study.} compared with the graft survival rates in 1985 and 2016, it can be seen that medical progress has greatly reduced the incidence of acute rejection over the past decades, but chronic rejection has resulted in a continuous decrease in the long-term survival rate of organs (photo source: reference [2]; Credit: Fadi G How to solve chronic rejection and improve the long-term survival rate of transplanted organs is of great significance to patients and organ donors.in this study, scientists studied the response of innate immune cells to organ transplantation.we know that the immune system can be divided into innate immunity and adaptive immunity.when foreign substances appear in the body, innate immune cells first detect the signal and then activate the adaptive immune system.and the immune system remembers foreign invaders so that they can be repelled more quickly the next time they encounter the same situation. the "memory" ability of the immune system provides us with long-term protection against bacterial viruses, but also brings about rejection of transplanted organs. for a long time, immune memory has been considered as the unique ability of adaptive immune cells (such as T cells and B cells). however, this research team has made a surprising discovery in the genetically modified mouse organ transplantation model: two kinds of innate immune cells can also produce specific "memory" of antigenic molecules when they encounter foreign tissues, and then initiate immune response when they encounter foreign tissues. "the innate immune cells of mice, such as monocytes and macrophages, have never been thought to have memory in the past," stressed Professor Martin oberbarscheidt, one of the co authors. "We found that they can also remember foreign tissues, which is just as specific as adaptive immune cells, which is incredible. "} images of transplanted kidney tissue in mice showed that wild-type mice had more immune cells (blue) than those in genetically modified mice (photo source: reference [1]). Subsequently, molecular and genetic analysis showed that the host's innate immune cells could not do without a kind of recognition and memory function called pir-a (pairing) Immunoglobulin like receptors. when researchers block pir-a with a synthetic engineering protein or remove its gene from the host animal by genetic means, the memory response of these innate immune cells is eliminated. the experimental results are very encouraging. The survival time of transplanted kidney in mice can be more than 125 days. In contrast, in the control group without pir-a treatment of innate immune cells, the survival time of transplanted kidney in 80% of mice is less than 20 days. in addition, similar results were obtained in mice with heart transplantation. } gene knockout or pir-a blocking significantly reduced the rejection of transplanted kidney in mice (photo source: reference [1]). Dr. lakkis pointed out: "to understand exactly how the innate immune system works can open the door to the development of highly specific drugs, so that we can get rid of the extensive immunosuppressive drugs with serious adverse effects. "according to oberbarnscheidt, the significance of this discovery is not only in the field of organ transplantation:" a wide range of diseases, including cancer and autoimmune diseases, can benefit from this insight. it changes our view of the innate immune system. "References: [1] Hehua Dai et al., (2020) PIRS mediate innate myeloid cell memory to nonself MHC molecules. Science. Doi: 10.1126/ science.aax4040 [2] Immune system discovery could end chronic organ rejection. Retrieved May 11, 2020, from