"Chicken novel leukocyte immunoglobulin-like receptor subfamilies B1 and B3 are transcriptional regulators of MHC class I genes and signaling pathways"

Authors: TROUNG, ANH - Chung-Ang University; HONG, YEOJIN - Chung-Ang University; LEE, JANGGEUN - Chung-Ang University; LEE, KYUNGBAEK - Chung-Ang University; Lillehoj, Hyun; HONG, YEONG HO - Chung-Ang University

Submitted to: Molecular Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/4/2018
Publication Date: 10/26/2019
Citation: Troung, A.D., Hong, Y., Lee, J., Lee, K., Lillehoj, H.S., Hong, Y. 2019. "Chicken novel leukocyte immunoglobulin-like receptor subfamilies B1 and B3 are transcriptional regulators of MHC class I genes and signaling pathways". Molecular Immunology. 32:614-620.

Interpretive Summary: Limited information on host immune system and the function of many immune components hinders rapid progress in developing treatment strategies for infectious diseases in poultry. In this report, ARS scientists collaborated with scientists at a South Korean university to identify one of key cell receptors that play important roles in host immune communication. This receptor is called leukocyte immunoglobulin-like receptors (LILRs) in mammalian species and is the target protein that interacts with the chicken leukocyte antigen (HLA) class I molecules and non-HLA ligands and are well-characterized in mammals. In this paper, the authors describe poultry LILRs and show that these receptors in poultry also interact with major histocompatibility complex (MHC) class I and non-classical ß2-microglobulin (ß2m) similar to mammals. Also, the authors describe gene cloning and structural and functional analysis of these receptors. Findings are important for better understanding of poultry immune system and understanding these innate immune receptors will facilitate disease prevention strategies.

Technical Abstract: The inhibitory leukocyte immunoglobulin-like receptors (LILRBs) play an important role in innate immunity. The present study represents the first description of the cloning and structural and functional analysis of LILRB1 and LILRB3 isolated from two genetically disparate chicken lines. Amino acid homology and phylogenetic analyses showed that the homologies of LILRB1 and LILRB3 in the chicken line 6.3 to those proteins in the chicken line 7.2 ranged between 97-99%, while homologies between chicken and mammal proteins ranged between 17-70%, and 16-20%, respectively. Our findings indicate that LILRB1 and LILRB3 subdivided into two groups based on the ITIM motifs present in the transmembrane domain. Chicken line 6.3 has two ITIM motifs of the sequence LxYxxL and SxYxxV while line 7.2 has two ITIM motifs of the sequences LxYxxL and LxYxxV. These motifs bind to SHP-2 that plays a regulatory role in immune functions. Moreover, our data indicate that LILRB1 and LILRB3 associated with and activated MHC class I and ß2-microglobulin and induced the expression of transporters associated with antigen processing, which are essential for MHC class I antigen presentation. This suggests that LILRB1 and LILRB3 are transcriptional regulators, modulating the expression of components in the MHC class I pathway and thereby regulating immune responses. Furthermore, LILRB1 and LILRB3 activated JAK2/TYK2, STAT1/3, and SOCS1 genes expressed in HD11 cells, which induced Th1, Th2, and Th17 cytokines. Taken together, these data indicate that LILRB1 and LILRB3 are innate immune receptors associated with SHP-2, MHC class I, ß2-microglobulin, and they activate the JAK/STAT signaling pathway. Thus, our study provides novel insights into the regulation of immunity and immunopathology.