Cell: Myelin cell immune signaling hub - TREM2.

Alzheimer's disease!---- obesity-related metabolic syndrome and tumors are the leading causes of death today.the latest research shows that in these disease sourcing situations, TREM2 acts as a pathologically induced immune signal hub that responds to tissue damage and performs immune remodeling.play an irreplaceable role in the reunification of disease development.Ido Amit, Aleksandra Deczkowska and Assaf Weiner of the Weizmann Institute in Israel published on Cell an opinion article entitled The Physiology, Pathology, and The Tes Therapeutic S. Of The TREM2 Signaling Pathway.this article gives an overview of TREM2 signal transduction and its role in pathology, in order to develop the future direction of related research.in recent years, more and more studies have shown the central role of myelin-derived cells in various pathology.where myelin cell trigger receptor receptor receptor on myeloid cells-2 TREM2 is considered a pathologically induced immune signal hub.TREM2 is the receptor of a variety of ligands, most of which are markers of tissue damage.in physiological state, the activity of TREM2 is limited to specific tissues, while in pathological states, the TREM2 signaling pathway becomes the immune signal hub for perceived tissue damage and inhibits damage.these findings have also inspired academics and industry to explore strategies to regulate TREM2 activity and the possibility of treating diseases.Trem2 ligand and signal transduction: Known and unknown TREM2 belongs to the immunoglobulin superfamily and is a transmembrane receptor.TREM2 has a variety of ligands, mainly free binding negatively charged molecules on the membrane, including bacterial composition, DNA, lipoproteinand and phospholipids.TREM2 has an extracellular domain that contains a V-type immunoglobulin domain, a short-cell outer domain, a transmembrane helical domain, and a short cytoplasm tail, with no signal transduction and transport matrix.TREM2 can bind to the joint proteins DAP12 and DAP10 in mouse macrophages.TREM2 binds to the ligand, the coreceptor molecule is phosphorylation, collecting the signal transduction molecule within the cell (DAP12 for Syk, DAP10 for PI3K).in mouse macrophages, calcium ion mobilization requires DAP12, dAP10, which is important for AKT1 and ERK activation.current research shows the TREM2 signal and its complexity. first of all, TREM2 is combined with different ligands to regulate the direction of TREM2 signal transduction and can produce different effects. a wide range of ligands, complicating the combination of TREM2. low affinity ligands promote DAP12, which inhibits cell activation through SHP-1-Syk. in cases of tissue damage such as bacterial infection, pathogen invasion, and cell death, TREM2 binds to surface phospholipids and cell fragments. in the Alzheimer's brain, TREM2 can bind directly to the pathological beta-amyloid protein and form plaques with amyloid proteins. secondary intracellular biological processes can also regulate TREM2 signal transduction. the downstream signal regulation of TREM depends on the active state of DAP10 and DAP12, which is also determined by cell type and cell state. TREM2 signals are most correlated with tissue damage and disease pathology, so the interoperability between TREM2 signals and the signal pathways of hazard signal activation is very important. TAM receptors associated with the swallowing of apoptosis fragments can bind to TREM2 expressed in small glial cells, but little is known about the interaction between the two signals. TREM2 signal regulation can also be achieved by controlling its expression. studies have found that stimulation of PPAR, LXR, and RXR promotes expression of TREM2 and other phagocytod-related receptors in mice. mice, TREM2 can be inhibited by micro-RNA miR-34a. TREM2 also indicates an uptick when NF-B is activated. significantly increased expression in the brains and eyes of Alzheimer's patients with macular lesions. TREM2 signal activation and regulation is a complex process, mainly depending on the tissue microenvironment and intracellular state. more research is needed on the regulation of TREM2 signals and how they interact with coreceptors. in order to better understand the integration of TREM2 signals into other cellular biology processes, more efforts are needed to study the downstream mechanisms of TREM2 signal activation with the molecular connections of TREM2-dependent, participated phenotymatic transformation processes. The physiological effects of the TREM2 signal and its regulatory strategy TREM2 in a specific environment, i.e. in the brain and bones, TREM2 plays a very important role in tissue development and functional maintenance, and TREM achieves this function by expressing small glial cells and bone-breaking cells in myelin cells. single-cellRNA transcriptome sequencing found that TREM-specific expression is found in a small number of human tissue-specific macrophages, such as the brain (small glial cells), adipose tissue, adrenal glands, and macrophages in the placenta. but the role of TREM2 in some specific tissue macrophages has yet to be determined. at the cellular level, TREM2 signals induce cell phenotypes and functional changes in different contexts, a process that relies on the various biological processes involved in TREM2, including phagocytosis, metabolic processes, cell survival, and inflammatory effects. . phagocytosis and metabolic TREM2 missing mice or in vitro cultured TREM2 missing cells will reduce the phagocytosis of apoptotic cell fragments, lipoproteins, bacteria, etc. expressing TREM2 in CHO cells induces phagocytosis. but the mechanism of swallowing on TREM2 is not yet clarified. TREM2-induced phagocytosis in CHO cells depends on the kinetic protein recombination mediated by Rac and Cdc42 and Syk kinase activity. however there was no significant difference in the effect of small glial cells in mice missing from TREM2 to eat apoptosis fragments. but cholesterol outflows are significantly inhibited, leading to the accumulation of cholesterol esters and cholesterol oxide esters. these metabolic intermediates also accumulate in Alzheimer's disease and atherosclerosis plaques. current research can only show that TREM2 is involved in the apoptosis cell removal process, but the mechanism is very little known. inflammatory resistance to devouring apoptosis cell fragments is itself a mechanism to prevent secondary necrosis and suppress the release of endogenous prosthesis warning signs. key molecules in the apoptosis removal process can cause mice to develop chronic inflammatory diseases. studies have shown that TREM2 promotes phagocytosis and inhibits the immune activation process. studies at the molecular level have shown that small glial cells and macrophages promote the expression of anti-inflammatory genes in a way that Isitadown relies on. but TREM2 can also bind to bacterial products, theoretically leading to immune activation. it is necessary to focus on the interoperability between bacterialally activated signals and other immune signals, and multiple signals, combined with integration of cell types and states, resultin in the phenotype results of TREM2 and ligand interactions in complex invivia environments. the study of cell survival studies shows that when in vitro environmental growth factors are depleted, The TREM2 signal can promote macrophage survival, and in stressful environments such as tissue damage and inflammation can also promote macrophage survival. small glial cells with missing or dysfunctional TREM2 reduce glucose use, underlying glycoenzyme seisthing and lower levels of ATP production, leading to lower cell metabolism and lower survival rates. TREM2 signal is essential for bone-breaking cell differentiation and maturation. The number of bone-breaking cells in mice missing TREM2 decreased significantly. TREM2 is also necessary for lipid-related macrophages that induce mononucleosis sources. these cells are located in adipose tissue and regulate metabolic syndrome in obesity. TREM2 is a signalhub for regulating cells from a variety of myelin sources. But under physiological conditions, TREM2 deficiency is observed only in specific tissues with adverse consequences, and in pathological cases, the role of TREM2 is more important. Trem2's different roles in the disease Alzheimer's disease builds a neurodegenerative mouse model of TREM2 deficiency found its specific role in these diseases. TREM2 promotes the survival of small glial cells and shifts to disease-related small glial cell types. this cell type limits plaque development by forming a physical barrier around amyloid protein aggregates, the main characteristics of this cell subtype are high expression of phagocytosis and lipid metabolism-related genes. observed changes in TREM2 expression levels in a variety of human neurodegenerative diseases, further highlighting the importance of TREM2 in human neurological diseases and its potential as a potential therapeutic target. soluble TREM2 soluble STREM2 is a by-product of protein hydrolysis or selective splifying. soluble TREM2 (sTREM2) can be detected in human cerebrospinal fluid, and in cerebrospinal fluid in patients with a variety of neurological diseases, the level of sTREM2 is significantly increased. studies have shown that sTREM2 levels reflect changes in the function of small glial cells, which also vary with the progression of aging and AD. asymptomatic period of disease sTREM2 levels are low, peak at early symptoms, correspond to early activation of small glial cells, and progression period is slightly reduced. sTREM2 in stress conditions can promote myelin cell survival, which also suggests its therapeutic potential. 's role in tumors is increasingevidence that TREM2 plays an important role in inhibitory cells of tumor-related macrophages and myelin sources. studies have shown an increase in the expression of TREM2 in tumor-related macrophages and peripheral blood mononucleocells in lung cancer models. and its expression was positively correlated with tumor progression. TREM2-positive myelin cells can significantly inhibit The proliferation of T cells. there was a significant negative correlation between TREM2 levels and prognosis in 317 patients with stomach cancer. concluded that TREM2 plays an important role in immunosuppressive in tumor microenvironment. obesity, fatty liver and atherosclerosis obesity, fatty liver and atherosclerosis are characterized by chronic low levels of inflammation and accumulation of apoptosis and protein aggregation. TREM2 plays a key role in these pathological processes by promoting phagocytosis and resisting inflammation to suppress tissue damage. as mentioned earlier, TREM2 can also be involved in regulating metabolic syndrome in obese patients through the maturation differentiation of lipid-related macrophages. fat-related macrophages can reshape adipose tissue and inhibit fat cell growth. macrophages found in atherosclerosis and fatty liver have found that TREM2 has the same effect. all of these suggest the potential for TREM2 as a target for the treatment of related diseases. TREM2's strategic TREM2 signals are becoming signalhubs for diseases such as Alzheimer's disease, metabolic syndrome and tumors. there are many potential interventions that can target the TREM2 pathway as a therapeutic target. One of the most prominent methods of is to directly target the structural domain activated by a specific monoclonal antibody or small molecule to the receptor, thereby preventing or activating downstream signal transduction. targets TREM2 in Alzheimer's disease to activate the receptor, stimulate small glial cells to devour and remove amyloid deposits. another potential intervention strategy is to guide tissue-specific TREM2 ligands to where they are needed to achieve activation. however, this strategy requires more investment due to the limited understanding of TREM2 ligands. the basic principle of these strategies is to enhance their signal transduction by activating TREM2, thereby promoting the functional activity of macrophages and small glial cells. is the opposite in tumors, and TREM2's anti-inflammatory and immunosuppressive activities promote tumor growth and immune escape. in tumors, it is necessary to block The transduction of TREM2 signals or deplete TREM2-myelin cells to activate the T-cell-mediated antitumor immune response. in recent years researchers have focused on the central role of TREM2 in myelin cells in various pathological processes. the study of the function and regulation of the central hub of TREM2 pathological signals is beneficial to the development of effective immunotherapy for myelin-mediated diseases. .