Identification and functional characterization, including cytokine production modulation, of the novel chicken Interleukin-11

Abstract

Interleukin (IL)-11 plays an important role in the immune system. However, IL-11 has not yet been characterized in avian species, including chickens. This study is the first to clone and functionally characterize chicken IL-11 (chIL-11). Multiple alignments and phylogenetic tree comparisons of chIL-11 with IL-11 proteins from other species revealed high levels of conservation and a close relationship between chicken and Japanese quail IL-11. Our results demonstrate that chIL-11 was a functional ligand of IL-11RA and IL-6ST in chicken HD11 and OU2 cell lines, as well as activated and regulated JAK-STAT, NF-κB, PI3K/AKT, and MAPK signaling pathways in chicken cell lines. In addition, chIL-11 inhibited nitric oxide production, affected proliferation of both tested cell lines, inhibited Type 1 and 17 T helper (Th) cytokine and IL-26, IL-12, and IL-17A-induced interferon-γ production, and enhanced Th2 cytokine (IL-4 and IL-10) production. Taken together, functional analysis of chIL-11 revealed it bound to IL-11RA and IL-6ST and activated the JAK-STAT, NF-κB, and MAPK signaling pathways, which resulted in modulation of Th1/Th17 and Th2 cytokine production in chicken HD11 and OU2 cell lines. Overall, this indicates chIL-11 has a role in both the innate and adaptive immune system.

Keywords: Anti-inflammatory; Chicken; Interleukin-11; JAK/STAT; NF-κB; Pathways.