Functional analyses of the interaction of chicken interleukin 23 subunit p19 with IL-12 subunit p40 to form the IL-23 complex

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-23 alpha with other known IL-23 alpha amino acid sequences revealed regions of amino acid conservation.. The homologies of ChIL-23 alpha, IL-12p35, and similar mammalian subunits ranged between 26% and 42%. ChIL-23 alpha 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-kappa B, C/EBP alpha-beta, 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-12R131 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-12RP receptor expression, and activates the JAK/STAT signaling pathway that results in the interaction of ChIL-23 alpha with ChIL-12p40 to form the novel. ChIL-23 complex. Our results provide novel insights into the regulation of immunity, inflammation, and immunopathology.