Figure 1.

Structure, ligands, signal transduction pathways, and upstream regulatory mechanisms of LILRBs. (A) Top: Bubble chart displaying ligands of LILRB1-5, ordered by their introduction sequence in text, with columns representing corresponding LILRB receptors. Bottom: Domain architecture of individual LILRB receptors: extracellular Ig-like domains (red), transmembrane regions, and intracellular ITIMs (yellow). The dashed circle indicates that the functional role of this ligand-receptor interaction remains controversial. (B) Canonical LILRB-mediated downstream signaling pathway: ① Ligand binding to LILRBs triggers ② Lyn kinase autophosphorylation; ③ phosphorylates ITIM motifs in intracellular domains, leads to ④ recruitment and activation of SHP1/2, which ⑤ dephosphorylate downstream signaling proteins, ultimately ⑥ modulating downstream signaling cascades and cellular functions. (C) A polymorphism at c.59G in the 5'-UTR region modulates LILRB2 expression. (D) Differential promoter usage of LILRB1 in ① lymphocyte versus ② monocyte results in an additional exon in lymphocyte that suppresses protein translation. (E) Transcriptional regulation of LILRB1 and LILRB2 by epigenetic modifications, including ① histone acetylation and ② DNA methylation in promoter regions. (F) Post-translational regulatory mechanisms: ① FTO enhances LILRB4 expression via m6A demethylation, ② miR-103a-2-5p suppresses LILRB3 expression through mRNA degradation. (G) LILRB expression modulation by intercellular crosstalk, cytokines, pharmacological agents, and microbial infections.