Studies have revealed that cell death regulates the stability of the immune system

cell death regulates systemic lymphocyte growth disorders.
On May 19th, Cell Report published online the results of
Shanghai Institute of Nutrition and Health Researcher Zhang Hai corps, which revealed that mice with RIPK3 protein mutations can lead to the absence of RIPK1-RIPK3 interactions, thereby inhibiting the occurrence of procedural necrotic necrotasia in internal and external cells.
, the researchers found that in the FADD knock-out mouse model, the RIPK3 protein mutation also led to severe autoimmune lymphocyte growth syndrome. Zhang Haibing said that this provides a theoretical basis and potential targets for the treatment of related diseases.autoimmune lymphocyte growth syndrome is an autoimmune disease characterized by lymphocyte growth. The cause of the disease is the blocking of the path of death of lymphocytes, resulting in the development of lymphocytes stable state is destroyed, manifested in lymph node swelling, spleen swelling, lymphoma and other autoimmune diseases.
Zhang Haibing explained that the disease occurs when the body's normal apoptosis and procedural necrosis are destroyed.
cytocytosis is a new type of cyto-inflammatory death, characterized by the formation of necrosis small bodies by cytocytosine proteins and the release of contents of cell membrane formation hole rupture. Necrotic small bodies are mainly composed of the subject interaction protein kinases 1 and 3 (RIPK1, RIPK3), riPK1 and RIPK3 through the functional domain RHIM to form a polyprotein complex. At present, the physiological function and mechanism of RIPK3 protein RHIM function domain are not clear.
Zhang Haibing team through in-body cell experiments found that the expression of human and mouse sources of RIPK3 protein can induce apoptosis of cells, through the mutation RIPK3 protein RHIM functional domain of important points, not only to prevent the emergence of RIPK1/ RIPK3 protein polypolymer, but also to prevent apoptosis and cell program necrosis.
, in-body experimental results show that the mutation point can regulate the RHIM functional domain of RIPK3 protein, thus affecting cell death function. "That is, both the human source and the mouse source site can disrupt the function of RHIM-mediated RIPK3 polygene to cause cell death." Zhang Haibing told China Science Daily.to study the in vivo function of the RIPK3 protein RHIM functional domain, the researchers used CRISPR-Cas9 to model mice with specific mutations. Immuno-co-precipitation experiments showed that the RIPK3 protein could not interact with RIPK1 after point mutation.
to further confirm the effect of the mutation on cell necrossion, the researchers introduced the mutation in the FADD gene knock-out mouse model. It was found that mice that were due to die from embryonics survived and reached adulthood.
Zhang Haibing explained that FADD knocks out mice that die from excessive cell necrotization about 10 days after embryo development. The point mutation of RIPK3 could save the mouse embryo from being knocked out by FADD and survive into adulthood. "This proves that the RIPK3 protein RHIM functional domain played a key role in interstitional cell procedural necrotasia in the body."
note that the HADD knock-out mice that were due to embryo death survived the RIPK3 mutation, but suffered from systemic lymphocyte growth. Interestingly, on the basis of THEDD knock-out mice, RIPK3-point mutant mice had a more serious disease than the RIPK3 gene.
, on the basis of FADD knock-out, RIPK3-point mutant proteins mediate inflammatory responses that promote systemic lymphocyte growth in mice. "Zhang Haibing speculates that this may suggest that the cell inflammatory response triggered by RIPK3 is dependent on the protein skeleton of RIPK3, rather than on point mutations." As a result, after the RIPK3 mutation, the protein skeleton is still there, the inflammatory response is still there, and the disease is more severe. In , based on the above experiments, the researchers found that further knocking down RIPK1 could alleviate systemic lymphocyte growth.
this shows that RIPK3's RHIM functional domain not only played a key role in mediated cell procedural necrotic signaling path, but also regulated lymphocyte development and immune stability through interaction with RIPK1. "This provides a theoretical basis and new targets for the treatment of related autoimmune diseases." Zhang Haibing said.
RIPK3 not only mediates programmed necrotasia of cells, but also the inflammatory response. In response,
Wang Haikun, a researcher at the Pasteur Institute in Shanghai, told The China Science Journal that the study revealed the role of RIPK3's RHIM domain in cell death and systemic lymphocyte growth disease by building mice with mutations in the RIPK3 protein RHIM domain, which is different from previously reported.
" also provides a new animal model for further study of the biological significance of the different domains of the key molecule RIPK3 in this field. Wang Haikun said.
next, Zhang Haibing's research team will continue to study the interaction between RIPK3's point mutation and RIPK1 to explore its mechanism of regulation of cell death signaling pathping and inflammation. (Source: Xin Yu, China Science Journal)
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