RAET1E Mouse
Description
Immunological Functions and Interactions
RAET1E modulates immune responses through NKG2D receptor engagement on NK cells, T cells, and macrophages:
NKG2D-Mediated NK Cell Activation
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Stress signaling: RAET1E is upregulated on stressed, transformed, or infected cells, marking them for NK cell-mediated elimination .
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Chronic exposure: Prolonged interaction with RAET1E-expressing dendritic cells (DCs) induces NKG2D downregulation on NK cells, impairing tumor rejection and antiviral responses .
Table 2: Functional Consequences of RAET1E-NKG2D Signaling
| Context | Outcome | Source |
|---|---|---|
| Tumor surveillance | Impaired NK cell cytotoxicity due to NKG2D downregulation | |
| Viral infection | Enhanced NK cell activation (e.g., mCMV-encoded m18 induces RAE-1) |
Disease-Associated Expression
RAET1E is implicated in autoimmune and inflammatory diseases:
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Experimental autoimmune encephalomyelitis (EAE): Induced in spinal cord macrophages and microglia, correlating with disease progression .
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Atherosclerosis: A mutation in the Raet1e promoter increases atherosclerotic lesion formation in murine models .
Table 3: Disease Models and RAET1E Expression
| Disease | Expression Pattern | Mechanism | Source |
|---|---|---|---|
| EAE | Macrophages, microglia (proliferating cells) | M-CSF-dependent induction | |
| Atherosclerosis | Aortic endothelial cells, macrophages | Promoter mutation (QTL mapping) |
Regulatory Mechanisms
RAET1E expression is tightly controlled by cellular and viral factors:
Cellular Regulation
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Proliferation: E2F transcription factors drive Raet1e transcription during cell division, as observed in fetal brain cells and cancer models .
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Inflammation: M-CSF stimulates RAE-1 expression in microglia during neuroinflammation .
Viral Modulation
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Murine cytomegalovirus (mCMV): Encodes protein m18, which binds the Raet1e promoter (-95 to -85 bp) to induce expression, enhancing NK cell activation .
Table 4: Key Regulatory Pathways
Genetic Polymorphisms
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Human disease: RAET1E polymorphisms correlate with premature coronary artery disease and cardiometabolic risk in Mexican populations .
Therapeutic Targeting
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Cancer immunotherapy: Modulating RAET1E expression could enhance NKG2D-mediated tumor clearance, though chronic exposure risks NK cell exhaustion .
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Autoimmunity: Inhibiting RAE-1 in macrophages/microglia may reduce neuroinflammatory damage .
Murine Models
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CD11c-Rae1 mice: Conditional expression in DCs enables study of NK-DC crosstalk. Key findings include reversible NKG2D downregulation and impaired tumor rejection .
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Transgenic systems: Rosa26-LSL-Raet1e knock-in mice paired with Cre drivers (e.g., CD11c-Cre) allow tissue-specific expression .
Recombinant Proteins
Product Specs
Product Science Overview
RAET1E is a cell surface glycoprotein composed of an external α1α2 domain, a transmembrane segment, and a C-terminal cytoplasmic tail . Unlike other RAET1 proteins, RAET1E has type I membrane-spanning sequences at its C-terminus rather than glycosylphosphatidylinositol anchor sequences . This protein functions as a ligand for the NKG2D receptor, which is expressed on the surface of several types of immune cells .
The interaction between RAET1E and the NKG2D receptor plays a crucial role in both innate and adaptive immune responses. It mediates natural killer (NK) cell cytotoxicity and T cell-mediated cytotoxicity, contributing to the regulation of immune responses .
RAET1E is expressed in various tissues, including the mucosa of the esophagus, skin, testicles, and olfactory zone of the nasal mucosa . The expression of RAET1E is induced by stress signals, making it a stress-induced ligand for the NKG2D receptor . This stress-induced expression is significant in the context of immune surveillance, where cells under stress, such as those infected by viruses or undergoing transformation, can be targeted by NK cells and cytotoxic T lymphocytes.
The recombinant form of RAET1E, particularly in mouse models, is widely used in research to study its role in immune responses. By using recombinant proteins, researchers can investigate the specific interactions between RAET1E and the NKG2D receptor, as well as the downstream effects on immune cell activation and cytotoxicity. This research is essential for understanding the mechanisms of immune surveillance and developing potential therapeutic strategies for diseases such as cancer and viral infections.
RAET1E has been associated with various diseases, including familial temporal lobe epilepsy . Its role in immune responses also makes it a potential target for immunotherapy. By modulating the interaction between RAET1E and the NKG2D receptor, it may be possible to enhance the immune system’s ability to target and eliminate cancer cells or infected cells.
