"Leukocyte Immunoglobulin-like receptors A2 and A6 are expressed in macrophages and modulate cytokine production by activating multiple signaling pathways"

Authors: TRUONG, ANH DUC - Chung-Ang University; RENGARAJ, DEIVENDRAN - Chung-Ang University; HONG, YEOJIN - Chung-Ang University; TRAN, HA THI THANH - National Institute Of Veterinary Research; DANG, HOANG VU - National Institute Of Veterinary Research; NGUYEN, VIET KHONG - National Institute Of Veterinary Research; Lillehoj, Hyun; HONG, YEONG HO - Chung-Ang University

Submitted to: Journal of Animal Science and Biotechnology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/4/2018
Publication Date: 9/11/2018
Citation: Truong, A., Rengaraj, D., Hong, Y., Tran, H., Dang, H., Nguyen, V., Lillehoj, H.S., Hong, Y. 2018. "Leukocyte Immunoglobulin-like receptors A2 and A6 are expressed in macrophages and modulate cytokine production by activating multiple signaling pathways". Journal of Animal Science and Biotechnology. https://doi.org/10.3390/ijms19092710.
DOI: https://doi.org/10.3390/ijms19092710

Interpretive Summary: Immune cells express various cell surface molecules which they use to communicate with stimulating agents. The leukocyte immunoglobulin-like receptor (LILR) family represents one such group of cell surface receptors and consists of members that play inhibitory or activating roles on the genes of the proteins involved with the immune system. In order to better characterize poultry immune system, ARS scientists collaborated with scientists from a Korean university and showed that there is high conservation in molecular sequences between mammalian and poultry LILR, especially poultry LILRA2 and LILRA6 with mammalian proteins. Furthermore, Poultry LILR receptors play a regulatory role in immune function and activate key signaling pathways which are necessary to activate poultry immune system. The results of this study enhance our understanding of how various immune cells communicate with each other to engender effective immune response to pathogens.

Technical Abstract: Background: The activating leukocyte immunoglobulin-like receptors (LILRAs) play an important role in innate immunity. However, most of the LILRA members have not been characterized in avian species including chickens. The present study is the first attempt at cloning, structural analysis, and functional characterization of two LILRAs (LILRA2 and LILRA6) in chickens. Results: Multiple sequence alignments and construction of a phylogenetic tree of chicken LILRA2 and LILRA6 with mammalian proteins revealed high conservation between chicken LILRA2 and LILRA6, and a close relationship between the chicken and mammalian proteins. The mRNA expression of LILRA2 and LILRA6 was high in HD11 macrophages and the small intestine compared to that in several other tissues and cells tested. To examine the function of LILRA2 and LILRA6 in chicken immunity, LILRA2 and LILRA6 were transfected into HD11 cells. Our findings indicated that LILRA2 and LILRA6 are associated with the phosphorylation of Src kinases and SHP2 that play a regulatory role in immune functions. Moreover, LILRA6, but LILRA2 did not, associated with and activated MHC class I, ß2-microglobulin, and upregulated transporters associated with antigen processing gene (TAP1-2). Furthermore, both LILRA2 and LILRA6 activated JAK-STAT, NF-'B, PI3K/AKT, and ERK1/2 MAPK signaling pathways, and induced Th1-, Th2-, and Th17-type cytokines, and Toll-like receptors. Conclusions: This study indicates that LILRA2 and LILRA6 are essential for macrophage-mediated immune responses, and they have the potential to complement the innate and adaptive immune system against pathogens.