Sepsis is one of the leading causes of hospital mortality, and its pathological mechanisms remain unclear. Currently, sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The uncontrolled inflammation occurring in sepsis leads to multiple organ damage and shock, ultimately resulting in patient death. However, the regulatory mechanisms that limit excessive inflammation are still poorly understood. Over the past 40 years, treatments targeting TLRs and inflammatory responses have been extensively explored in sepsis, with more than 100 clinical trials attempting to modulate systemic inflammatory responses by targeting endogenous mediators. However, the efficacy of most therapeutic targets has been unsatisfactory. Therefore, there is an urgent need to further explore the inflammatory regulatory mechanisms of sepsis to develop more effective treatments. Alexa Fluor 647-labeled SLAMF7/CRACC/CD319 Fc chimera protein can be used to quantitatively detect the expression levels and binding activity of SLAMF7 protein, providing a technical tool for sepsis research.
This study identified an immunoglobulin-like receptor called signaling lymphocytic activation molecule family-7 (SLAMF7) as a key inhibitory factor of inflammation during sepsis. In both sepsis patients and septic mice, SLAMF7 expression was significantly elevated on monocytes and macrophages. By collaborating with SHIP1, SLAMF7 attenuated TLR-dependent MAPK and NF-κB signaling activation in macrophages. SLAMF7 interacted with SHIP1 and TRAF6, inhibiting K63-linked ubiquitination of TRAF6. SLAMF7 prevented lethal sepsis and endotoxemia by downregulating pro-inflammatory cytokines in macrophages and suppressing inflammation-induced organ damage. These results reveal the negative regulatory role of SLAMF7 in polymicrobial sepsis and provide insights for sepsis treatment. Alexa Fluor 647-labeled SLAMF7/CRACC/CD319 Fc chimera protein can be used to study the interaction between SLAMF7 and downstream signaling molecules, offering a quantitative analysis tool for mechanistic research.
SLAMF7 is a member of the CD247 superfamily of immunoglobulin-like receptors and plays an important role in regulating the function of immune cells, particularly natural killer cells. Like other SLAMF members, SLAMF7 functions as a self-ligand receptor. SLAMF7 contains immunoreceptor tyrosine-based switch motifs (ITSMs) in its cytoplasmic domain, which are phosphorylated upon activation and recruit SH2 domain-containing molecules to transmit downstream signals. SLAMF7 has been shown to inhibit the expression of TNF and IL-12p70 in human monocytes. Additionally, SLAMF7 negatively regulates inflammation in certain infectious diseases, such as downregulating IFN-α-mediated CXCL10 production in chronic HIV infection. The tyrosine phosphorylation sites within SLAMF7's intracellular domain and SHIP1's phosphatase domain are essential for the interaction between SLAMF7 and SHIP1/TRAF6, as well as for SLAMF7-mediated regulation of cytokine production.
This study revealed the mechanism by which SLAMF7 collaborates with SHIP1 to inhibit TRAF6 ubiquitination and suppress pro-inflammatory cytokine production. SLAMF7 interacts with SHIP1 and TRAF6, inhibiting K63-linked ubiquitination of TRAF6. During innate immune responses, multiple negative effectors are induced and act as feedback loops to suppress inflammation caused by sepsis. The interaction between SLAMF7, SHIP1, and TRAF6 provides new insights into understanding the negative regulatory network in sepsis. By collaborating with SHIP1, SLAMF7 attenuates TLR-dependent MAPK and NF-κB signaling activation in macrophages, thereby limiting excessive inflammatory responses. This negative regulatory mechanism is crucial for maintaining immune homeostasis and preventing tissue damage in sepsis.
SLAMF7 plays a critical role in regulating macrophage inflammation. This study found that SLAMF7 expression was significantly elevated on monocytes and macrophages in both sepsis patients and septic mice. SLAMF7 prevents lethal sepsis and endotoxemia by downregulating pro-inflammatory cytokines in macrophages and suppressing inflammation-induced organ damage. In sepsis, pathogen clearance largely relies on pattern recognition receptors activating innate immune responses. Toll-like receptors (TLRs) play a key role in responding to exogenous pathogens and endogenous ligands, but excessive inflammatory responses can lead to organ failure and even death. SLAMF7 acts as a negative regulator, playing an important role in limiting excessive inflammatory responses. Alexa Fluor 647-labeled SLAMF7/CRACC/CD319 Fc chimera protein can be used to assess the expression levels and functional status of SLAMF7 on macrophage surfaces.
This study provides evidence that SLAMF7 is a key negative regulator of sepsis-induced inflammation, revealing the mechanism by which SLAMF7 collaborates with SHIP1 to inhibit TRAF6 ubiquitination and suppress pro-inflammatory cytokine production. The discovery of SLAMF7's regulatory role in sepsis and its interaction with TRAF6 and SHIP1 in downstream signaling may support the development of sepsis treatment strategies. Alexa Fluor 647-labeled SLAMF7/CRACC/CD319 Fc chimera protein offers a sensitive and efficient detection tool for studying SLAMF7 protein expression, distribution, and interactions, with applications in macrophage function evaluation and immune monitoring, among other areas.
Nanjing UA-Bio Technology Co., Ltd. (UA-Bio) has independently developed "Alexa Fluor 647-Labeled SLAMF7/CRACC/CD319 Fc Chimera Protein, Human" (Catalog No.: UA011261), a high-performance far-red fluorescent-labeled probe specifically designed for SLAMF7-targeted research and multiple myeloma immunotherapy evaluation. SLAMF7 (also known as CRACC or CD319) is a member of the signaling lymphocytic activation molecule family and is highly expressed on the surface of multiple myeloma cells, making it an important target for tumor immunotherapy. This protein is a chimera composed of the human SLAMF7 extracellular domain fused to the human IgG Fc fragment and labeled with Alexa Fluor 647. It efficiently binds to anti-SLAMF7 antibodies or affinity ligands, providing a stable and reliable standardized tool for CAR-T cell therapy evaluation, antibody drug screening, multiparameter analysis of multiple myeloma markers, and other applications.
| Core Advantages | Detailed Parameters / Functional Description |
|---|---|
| High Purity and Intact Bioactivity | The product is produced using internationally leading eukaryotic expression systems and highly standardized purification processes, validated by multidimensional quality control to ensure >95% purity and correct native conformation (retaining intact glycosylation modifications). The Fc chimera format enhances protein stability and proper folding. The Alexa Fluor 647 labeling process is optimized to ensure high labeling efficiency while maintaining high-affinity binding to antibodies, accurately simulating the antigenic properties of SLAMF7 on multiple myeloma cell surfaces under physiological conditions.-- |
| Far-Red Fluorescence and Multicolor Compatibility | Labeled with Alexa Fluor 647, this dye exhibits high fluorescence brightness, excellent photostability, and low background noise. With an excitation peak at ~650 nm and an emission peak at ~665 nm, it falls within the far-red region, effectively avoiding detection channels of common fluorophores like FITC and PE, supporting multicolor analysis in flow cytometry and multichannel imaging in fluorescence microscopy.-- |
| Exceptional Batch-to-Batch Consistency and Stability | Strict quality control is implemented throughout protein expression, labeling, and purification, combined with a comprehensive release testing system, ensuring consistent binding activity, uniform fluorescence intensity, and excellent long-term stability across batches. This provides reliable quality assurance for long-term and continuous SLAMF7-targeted research.-- |
| Ideal Tool for Multiple Applications | This protein performs excellently in various application systems, including CAR-T cell positivity rate detection by flow cytometry (supporting multicolor panel design), anti-SLAMF7 antibody/antagonist screening (e.g., activity evaluation of biosimilars like elotuzumab), competitive binding assays, multiparameter analysis of multiple myeloma markers, and flow cytometry. It is widely applicable to SLAMF7-targeted CAR-T cell therapy development, multiple myeloma diagnostic tool research, and drug activity evaluation.-- |
| Comprehensive Solutions and Professional Support | We provide thoroughly validated standard protocols, typical flow cytometry data, and detailed interpretation guides to help establish stable and reproducible SLAMF7-targeted molecular detection workflows. Nanjing UA-Bio's technical team offers professional consultation and support for research design, experimental optimization, and data analysis.-- |
Nanjing UA-Bio Technology Co., Ltd. is committed to providing cutting-edge, high-quality core reagents and tools for immunology, cell therapy, and innovative drug development. For detailed technical parameters, validation data, or application inquiries regarding "Alexa Fluor 647-Labeled SLAMF7/CRACC/CD319 Fc Chimera Protein, Human" (Catalog No.: UA011261), please feel free to contact us.
