The LILRB3 Knockout HMC3 Cell Line is a CRISPR/Cas9-edited knockout cell line generated from the HMC3 human microglial cell line. This stable loss-of-function model enables investigation of LILRB3, an inhibitory immune receptor, in microglial immune regulation and neuroinflammation. CRISPR/Cas9-mediated gene disruption abolishes LILRB3 expression, providing a tool to dissect LILRB3-dependent signaling pathways and their impact on myeloid cell function.
The HMC3 cell line is an SV40-immortalized human fetal microglial cell line that serves as a well-established in vitro model of resident central nervous system (CNS) immune cells. Microglia are the primary innate immune cells of the CNS, playing critical roles in neuroinflammation, synaptic pruning, and maintaining brain homeostasis. The HMC3 line retains many phenotypic and functional characteristics of primary microglia, including phagocytic activity and responsiveness to inflammatory stimuli. This makes it a valuable tool for studying microglial biology in health and disease. The engineered LILRB3 knockout variant enables the examination of how this inhibitory receptor modulates microglial functions.
LILRB3 (leukocyte immunoglobulin-like receptor subfamily B member 3) is a type I transmembrane protein containing immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in its cytoplasmic tail. Upon recognition of its ligands, which include major histocompatibility complex (MHC) class I molecules and angiopoietin-like proteins (ANGPTLs), LILRB3 recruits the tyrosine phosphatases SHP-1 and SHP-2. These phosphatases subsequently dephosphorylate key signaling intermediates, leading to suppression of NF-??B pathway activation and reduced production of pro-inflammatory cytokines. Through this mechanism, LILRB3 attenuates myeloid cell activation and phagocytosis, thereby contributing to immune tolerance. Its expression in microglia suggests a role in fine-tuning neuroinflammatory responses within the CNS.
In the context of microglial biology, loss of LILRB3 function is predicted to relieve inhibitory constraints on phagocytic activity and pro-inflammatory cytokine release. This knockout cell line therefore provides a powerful tool for modeling dysregulated microglial activation, which is implicated in various neuroinflammatory and neurodegenerative conditions. By comparing LILRB3 knockout HMC3 cells with wild-type controls, researchers can dissect the molecular basis of ITIM-mediated inhibitory signaling and its downstream effects on microglial effector functions. Such studies are particularly relevant for understanding diseases like Alzheimer’s disease, where aberrant microglial phagocytosis and chronic inflammation contribute to pathogenesis.
This LILRB3 knockout model is designed for a wide range of research applications, including microglial immune regulation studies, neuroinflammation modeling, and phagocytosis assays. Typical experimental workflows involve flow cytometry to confirm loss of LILRB3 surface expression, phagocytosis assays using fluorescently labeled substrates, cytokine ELISAs to measure secreted pro-inflammatory mediators, and western blotting to assess phospho-protein levels within the SHP-1/SHP-2/NF-??B axis. Co-immunoprecipitation experiments can further elucidate protein?Cprotein interactions involving LILRB3. For further information or technical support, please contact Ascent Research.
