Study reveals cell death regulates immune system stability

On May 19, The Cell-Report published the results of zhang Haibing's team, a researcher at the Shanghai Institute of Nutrition and Health of the Chinese Academy of Sciences, which revealed that mutations in the RIPK3 protein in mice can lead to the absence of RIPK1-RIPK3 interactions, thereby inhibiting the occurrence of procedural necrosis of the body and outer cellsin addition, researchers found that in FADD knockout mouse models, RIPK3 protein mutations also cause severeautoimmunelylylylylylyly lymphocytic hyperplasia syndromeZhang Haibing said that this provides a theoretical basis and potential target for the treatment of related diseasesmagic protein smothers cells to death and live
autoimmunelymphocyt hyperplasia syndrome is aautoimmunedisease characterized by lymphocyte hyperplasiaThe cause of the disease is that the death pathway of lymphocytes is blocked, which leads to the destruction of the development almost stable state of lymphocytes, as shown by the occurrence of lymph node swollen, spleen enlargement, lymphoma and other autoimmune diseasesZhang Haibing explained that the disease occurs when the body's normalapoptosisand procedural necrosis are destroyedcell procedural necrosis is a new type of cytophilis death, with cytoplasm proteins forming necrosis small bodies, cell membrane forming hole rupture release content as the main characteristicsNecrotic small bodies are mainly composed of receptor-interacting protein kinases 1 and 3 (RIPK1, RIPK3), and RIPK1 and RIPK3 form polyprotein complexes through functional domain RHIM At present, the physiological function and mechanism of THE RIPK3 protein RHIM functional domain are not clear Zhang Haibing team through in vitro cell experiments found that the expression of human and rat source RIPK3 protein can induce cell apoptosis, through the mutation OF RIPK3 protein RHIM functional domain of important sites, not only to prevent the emergence of RIPK1/RIPK3 protein polypolymer, but also to prevent apoptosis and cell programoblast Therefore, the results of in vitro experiments show that the mutation site can regulate the RHIM functional domain of the RIPK3 protein, thus affecting cell death function "That is to say, both the source and the rat source site can disrupt the RHIM-mediated RIPK3 polyfusion causes cell death Zhang Haibing told The China Science Daily mice survived but became ill
the researchers used CRISPR-Cas9 to build a mouse model of specific point mutations to study the invivy function of the RIPK3 protein RHIM functional domain The immunocoprecipitation experiment showed that the RIPK3 protein after the point mutation could not interact with RIPK1 to further confirm the effect of the mutation inhibiting cell necrosis, the researchers introduced the mutation in the FADD gene knockout mouse model It turned out that the mice that were supposed to be embryo-killing survived and lived into adulthood Zhang Haibing explained that FADD knocks out mice that die from excessive cell necrosis during about 10 days of embryonic development The point mutation of RIPK3 can save the mouse embryos that were knocked out of FADD and survive into adulthood "This proves that the RIPK3 protein RHIM functional domain plays a key role in mediated cell procedural necrosis in the body." noted that FADD knockout mice that should have died of embryos had systemic lymphocyte hyperplasia despite surviving the RIPK3 mutation Interestingly, on the basis of FADD knockout mice, the disease in THE RIPK3-point mutant mice was more severe than that of the RIPK3 gene " In other words, on the basis of FADD knock-off, RIPK3-point mutant protein sympathiser can mediate inflammatory responses to promote systemic lymphocyte hyperplasia in mice Zhang Haibing speculated that this may suggest that RIPK3 triggers a cell inflammatory response that relies on RIPK3's protein skeleton rather than point mutations "As a result, after the RIPK3 mutation, the protein skeleton is still there, the inflammatory response is still occurring, and the disease is more severe." "
two proteins still have "materials" to dig In addition, based on the above experiments, the researchers found that further knockout of RIPK1 could alleviate systemic lymphocyte growth this indicates that ripK3's RHIM functional domain not only plays a key role in the mediated cell programostationne signaling pathway, but also regulates lymphocyte development and immune stability through interaction with RIPK1 "This provides a theoretical basis and a new target for the treatment of related autoimmune diseases Zhang Haibing said RIPK3 not only mediates procedural necrosis of cells, but also mediates inflammatory reactions In response, Wang Haikun, a researcher at the Pasteur Institute of the Chinese Academy of Sciences in Shanghai, told the China Science Daily that the study revealed the role of RIPK3's RHIM structural domain in cell death and systemic lymphocytic growth disorder by building mutant mice that differ from previously reported RIPK3 protein RHIM " also provides a new animal model for further study of the biological significance of different domains of the key molecule RIPK3 Wang Haikun said next, Zhang Haibing's research team will continue to study the interaction between RIPK3's point mutation and RIPK1, and explore its mechanisms of action and inflammatory mechanisms for regulating cell death signaling pathways (
Bioon.com of Biological Valley)