unc-93 Antibody

Definition and Biological Role of UNC93B1

UNC93B1 (Unc-93 Homolog B1) is a transmembrane endoplasmic reticulum (ER) protein that chaperones nucleic acid-sensing TLRs (TLR3, TLR7, TLR9, TLR11, TLR12, TLR13) to endolysosomes, enabling pathogen recognition and immune activation . Deficiency in UNC93B1 disrupts TLR trafficking, impairing cytokine responses and increasing susceptibility to infections like Leishmania major and herpes simplex encephalitis .

Role in TLR Signaling and Infection Resistance

• TLR Trafficking: UNC93B1 binds TLR3, TLR7, and TLR9 in the ER, stabilizing them and enabling transport to endosomes . A histidine-to-arginine mutation (H412R) in UNC93B1 disrupts this interaction, impairing antiviral responses .

• Infection Models: UNC93B1 mutant mice exhibit heightened susceptibility to Leishmania major due to reduced IFN-γ and elevated IL-10. Rescue occurs via anti-IL-10R or recombinant IL-12 treatment .

Autoimmune and Neuroinflammatory Roles

• Autoimmunity: Gain-of-function UNC93B1 variants (e.g., T93I, R336C) hyperactivate TLR7, driving lupus-like inflammation in mice and humans . Heterozygous mutations suffice to cause systemic autoimmunity .

• Central Nervous System (CNS): UNC93B1 is expressed in microglia, neurons, and oligodendrocytes. It mediates neurotoxicity induced by microRNA let-7b via TLR7, implicating it in neurodegenerative diseases .

Molecular and Genetic Insights

• Gene and Protein Data:

  • Gene ID: 81622 (Human)

  • UniProt ID: Q9H1C4

  • Molecular Weight: ~67 kDa (predicted), ~70 kDa (observed)

• Pathways: MyD88-dependent TLR signaling, innate immune regulation .

Clinical and Therapeutic Implications

• Therapeutic Targets: Blocking UNC93B1-TLR interactions could mitigate autoimmune disorders. Conversely, enhancing UNC93B1 function might bolster antiviral responses .

• Biomarker Potential: Elevated UNC93B1 expression correlates with neuroinflammation and lupus nephritis .

Validation and Technical Considerations

• Specificity: Antibodies like ABIN6990887 and 28359-1-AP do not cross-react with UNC93A .

• Buffer and Storage: Most antibodies are stored in PBS with glycerol at -20°C .