Characterization and functional analyses of novel chicken leukocyte immunoglobulin-like receptor subfamily B members 4 and 5

Abstract

The inhibitory leukocyte immuno-globulin-like receptors (LILRBs) play an important role in innate immunity. Currently, no data exist regarding the role of LILRB4 and LILRB5 in the activation of immune signaling pathways in mammalian and avian species. Here, we report for the first time, the cloning and structural and functional analyses of chicken LILRB4–5 genes identified from 2 genetically disparate chicken lines. Comparison of LILRB4–5 amino acid sequences from lines 6.3 and 7.2 with those of mammalian proteins revealed 17 to 62% and 19 to 29% similarity, respectively. Phylogenetic analysis indicated that the chicken LILRB4–5 genes were closely associated with those of other species. LILRB4–5 could be subdivided into 2 groups having distinct immunoreceptor tyrosine-based inhibitory motifs, which bind to Src homology 2-containing tyrosine phosphatase 2 (SHP-2). Importantly, LILRB4–5 also upregulated the major histocompatibility complex (MHC) class I and β2-microglobulin gene expression as well as the expression of transporter associated with antigen processing 1–2, which play an important role in MHC class I activation. Our results indicate that LILRB4–5 are transcriptional regulators of the MHC class I pathway components and regulate innate immune responses. Furthermore, LILRB4–5 could activate the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway genes in macrophages and induce the expression of chemokines and T helper (Th)1, Th2, and Th17 cytokines. Our data suggest that LILRB4–5 are innate immune receptors associated with SHP-2, MHC class I, and β2-microglobulin. Additionally, they activate the JAK/STAT signaling pathway and control the expression of cytokines in macrophages.