Characterization and functional analysis of novel chicken leukocyte immunoglobulin-like receptor subfamily B member 4 and 5

Submitted to: Poultry Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/23/2019
Publication Date: 12/1/2019
Citation: Truong, A., Hong, Y., Tran, H., Dang, H., Nguyen, V., Pham, T., Lillehoj, H.S., Hong, Y. 2019. Characterization and functional analysis of novel chicken leukocyte immunoglobulin-like receptor subfamily B member 4 and 5. Poultry Science. https://doi.org/10.3382/ps/pez442.
DOI: https://doi.org/10.3382/ps/pez442

Interpretive Summary: Limited information on chicken immune molecules that mediate host immune response hinders progress in understanding host immune system of poultry and infectious diseases affecting poultry. In mammals, leukocyte immunoglobulin (Ig)-like receptor subfamily B members (LILRB) are are well known to be important members of host immune molecules. Recently, it was reported that LILRB proteins interact with human leukocyte antigen (HLA) class I molecules and induce the expression of cytokines. In order to investigate the homologue of LILRB mammalian LILRB molecules in chickens, ARS scientists and collaborators in a Korean university used a bioinformatics approaches. In this report, new findings on the genes which encode chicken LILRB are described and these scientists showed that chicken LILRB proteins play an important role in innate immunity. Availability of these genes and their encoded proteins should enable the detailed studies in the future that will reveal the underlying mechanisms of how these proteins work to protect the host from infectious diseases.

Technical Abstract: The inhibitory leukocyte immunoglobulin-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 two genetically disparate chicken lines. Phylogenetic analysis indicated that the chicken LILRB4-5 genes were closely associated with those of other species. LILRB4-5 could be subdivided into two groups having distinct immunoreceptor tyrosine-based inhibitory (ITIM) motifs, which bind to Src homology 2-containing tyrosine phosphatase 2 (SHP-2). Importantly, LILRB4-5 also up-regulated the major histocompatibility complex (MHC) class I and ß2-microglobulin (ß2m) gene expression as well as the expression of transporter associated with antigen processing (TAP) 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 ß2-microglobulin. Additionally, they activate the JAK/STAT signaling pathway and control the expression of cytokines in macrophages.