Molecular characterization and functional analysis of chicken interleukin 1 receptor 2 (chIL-1R2)

Authors: TRUONG, AD - National Institute Of Veterinary Research; TRAN, HTT - National Institute Of Veterinary Research; NGUYEN, HT - National Institute Of Veterinary Research; CHU, NT - National Institute Of Veterinary Research; HONG, YH - Chung-Ang University; Lillehoj, Hyun; DANG, HV - National Institute Of Veterinary Research; SONG, K-D - National Institute Of Veterinary Research

Submitted to: Poultry Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/5/2022
Publication Date: 2/1/2023
Citation: Truong, A., Tran, H., Nguyen, H., Chu, N., Hong, Y., Lillehoj, H.S., Dang, H., Song, K. 2023. Molecular characterization and functional analysis of chicken interleukin 1 receptor 2 (chIL-1R2). Poultry Science. https://doi.org/10.1016/j.psj.2022.102399.
DOI: https://doi.org/10.1016/j.psj.2022.102399

Interpretive Summary: Limited information on the function of various components of immune system of poultry hinders progress in developing various immunological strategies to mitigate disease responses in chickens. In this paper scientists at ARS, JeonBuk National University (Republic of Korea) and National Institute Veterinary Research (Vietnam) collaborated to identify the lymphocyte receptor called chicken IL-1R2 (chIL-1R) on various tissues of chickens and studied how this receptor interacts with its ligand chicken IL-1ß during inflammatory response in diseased chickens. The results showed that both chIL-1R1 and chIL-1R2 are essential for host immune response to pathogens such as highly pathogenic avian influenza virus (HPAIV) and their expression levels are controlled by IL-1ß/NF-'B/JNK/MEK-mediated signaling pathway with their expression levels increasing as early as 1 day after infection. Detailed gene expression analysis indicates that chIL-1R2 expression may respond specifically to viral infection and its expression level controlled by IL-1ß-mediated cellular responses. Correlation of their expression with viral disease state thus indicate that IL-1R2 (chIL-1R) could be used as a disease biomarker for early detection of HPAIV. Future studies focusing on the naturally occurring inhibitor involved in IL-1ß signaling activity by chIL-1R2 could open a door for novel immunotherapeutic discovery.

Technical Abstract: Interleukin-1 receptor type 2 (IL1R2) is a decoy receptor for exogenous IL-1; however, its functional role in chickens remains poorly understood. Herein, chicken IL-1R2 (chIL-1R2) was identified and functionally characterized in vivo and in vitro. The chIL-1R2 coding sequence includes 1,236 nucleotides encoding 412 amino acids, is highly conserved, and has a close relationship with mammals. It possesses three Ig-like domains in its extracellular region but lacks an intracellular signaling TIR domain. The recombinant chIL-1R2 protein was demonstrated to bind to the specific chicken IL-1ß antibody using ELISA. Additionally, the high chIL-1R2 mRNA expression in the spleen, lung, kidney, small intestine, and liver was compared with that in various tested healthy tissues. Our results showed that chIL-1R2 and chIL-1R1 expression was significantly upregulated in DF-1 cells under poly (I:C) stimulation and significantly downregulated in the presence of NF-'B, JNK, and MEK inhibitors, indicating that NF-'B, JNK, and MEK transcription factors are required for the regulation of chIL-1R1 and chIL-1R2 expression. In addition, p30-MAPK was regulated by chIL-1R1 but not by chIL-1R2 expression. Furthermore, chIL-1R2 increased as early as day 1, and then significantly decreased until day 3, while chIL-1R1 was dramatically upregulated in four organs of chickens infected with the highly pathogenic avian influenza virus (HPAIV). This indicates that chIL-1R1 and chIL-1R2 are essential for immune response and they have the potential to complement innate and adaptive immune systems against HPAIV. Our results suggest that chIL-1R2 expression is induced by viral infection and its expression is under the control of IL-1ß/NF-'B/JNK/MEK-mediated signaling pathway.