|Truong, Anh - Chung-Ang University|
|Hoang, Cong - Chung-Ang University|
|Hong, Yeojin - Chung-Ang University|
|Lee, Janggeun - Chung-Ang University|
|Lee, Kyungbaek - Chung-Ang University|
|Hong, Yeong - Chung-Ang University|
Submitted to: Molecular Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/11/2017
Publication Date: 12/11/2017
Publication URL: http://handle.nal.usda.gov/10113/5837972
Citation: Truong, A.D., Hoang, C.T., Hong, Y., Lee, J., Lee, K., Lillehoj, H.S., Hong, Y.H. 2017. Functional analyses of the interaction of chicken interleukin 23 subunit p19 with IL-12 subunit p40 to form the IL-23 complex. Molecular Immunology. 92:54-67. https://doi.org/10.1016/j.molimm.2017.09.019.
DOI: https://doi.org/10.1016/j.molimm.2017.09.019 Interpretive Summary: Lack of poultry immune reagents that can identify different components of chicken immune system hinders the progress in understanding the disease process and vaccine development against important poultry diseases. In this paper, ARS scientists collaborated with scientists in South Korea to identity a new chicken molecule which is important in protecting host against infectious pathogens. In this study, these authors describe the molecular cloning and the characterization of chicken molecule called IL-23 for the first time. This molecule is not conserved across different animal species and the detailed investigation of its molecular function revealed that they activate key molecular pathways which are critically involved in initiating inflammatory host response. A deeper understanding of the intracellular signal transduction pathways which are initiated by the ChIL-23 molecule will be necessary to better determine how the ChIL-23 activates immune-related gene expression in poultry. These results will facilitate developing a novel prevention strategy against poultry diseases.
Technical Abstract: This study represents the first description of the cloning of chicken IL-23p19 (ChIL-23a) and the function of the IL-23 complex in birds. Multiple alignment of ChIL-23a with other known IL-23a amino acid sequences revealed regions of amino acid conservation. The homologies of ChIL-23a, IL-12p35, and similar mammalian subunits ranged between 26% and 42%. ChIL-23a consisted of four exons and three introns; similar to those in humans and mice, and limited conservation of synteny between the human and chicken genomes was observed. Using bioinformatics tools, we identified the NF-'B, C/EBPa-ß, c-Jun, c-Rel, AP-1, GATA-1, and ER promoter sites in ChIL-23a. Moreover, IL-23a mRNA was more highly expressed than IL-12p40 and IL-12p35 mRNA in several organs of chickens infected with Salmonella. In addition, ChIL-23 complex are associated with IL-23R, IL-12Rß1 receptors; activate the JAK2/TYK2, STAT1/3, SOCS1 genes, and induced proinflammatory cytokines in immune cells. Collectively, these results indicate that ChIL-23 is a member of the IL-12 family, has proinflammatory properties related to IL-23R and IL-12Rß1 receptor expression, and activates the JAK/STAT signaling pathway that results in the interaction of ChIL-23a with ChIL-12p40 to form the novel ChIL-23 complex. Our results provide novel insights into the regulation of immunity, inflammation, and immunopathology.