IL-23 Bioassay, Propagation Model
Interleukin-23 (IL-23) was first described in 2000 when a computational screen identified a novel sequence (p19) that combined with the p40 subunit of IL-12 to create an active and composite cytokine. It is secreted by activated dendritic cells and possesses biological properties both distinct from and in common with IL-12.IL-23 is a member of the larger IL-12 cytokine family, which consists of IL-12, IL-23, IL-27, IL-35 and IL-39. This unique group of heterodimeric cytokines consists of an alpha chain subunit (p19, p28 or p35) and a beta chain subunit (p40 or Epstein-Barr virus induced gene 3), and signals through JAK/STAT pathways. IL-23 binds and signals through a heterodimeric receptor complex. The p19 subunit binds to IL-23R and p40 subunit to IL-12Rβ1. Similarly, the p35 and p40 subunits of IL-12 bind to IL-12Rβ2 and IL-12β1, respectively. The IL-23 receptor is found on natural killer cells, macrophages, memory T cells (Th17) and keratinocytes. In response to microbial pathogens and wound healing signals, IL-23 is secreted by activated dendritic cells and macrophages with subsequent neutrophil recruitment.Upon IL-23 binding to Th17 cells, signaling begins with tyrosine kinase 2 (TYK2) recruitment to IL-12Rβ1 and Janus kinase 2 (JAK2) recruitment to IL-23R. These kinases phosphorylate and activate signal transducer and activator of transcription 3 (STAT3), and to a lesser extent STAT4, STAT1 and STAT5 (2). Phosphorylated STAT3 complexes translocate to the nucleus, inducing expression of IL-17A, IL-23R and the transcription factor retinoid-related orphan receptor-γt, thus stabilizing the Th17 phenotype (3).Both IL-23 and IL-12 cytokines are involved in human T helper cell differentiation and survival. IL-12 binds anddirectly promotes the differentiation of naïve CD4+ T cells into T helper 1 cells. It is believed that IL-6, IL-1β andTGFβ are involved in the differentiation of human T helper 17 cells (Th17), while IL-23 is critical for their maturation,maintenance and pathogenicity (4-6).Ustekinumab is a humanized antibody that targets the p40 cytokine subunit and prevents IL-12 and IL-23 binding toIL-12Rβ1. It was FDA approved for the treatment of psoriasis in 2009, psoriatic arthritis in 2013 and most recently Crohn’s disease in 2016.Recent research has indicated IL-23 and the Th17 secretion of the pro-inflammatory cytokines IL-17, IL-22 and IL-21 are prominent contributors to the formation of psoriatic inflammation and plaques (8-10). By selectively targeting the IL-23p19 subunit, key therapeutic advantages may be achieved including preserving IL-12 Th1 pathogenic responses.The IL-23 Bioassay(Cat.# JA2511, JA2515) is a bioluminescent cell-based assay designed to measure IL-23 stimulation or inhibition. The IL-23 Bioassay Cells are provided in a thaw-and-use format as cryopreserved cells that can be thawed, plated and used in an assay without the need for cell propagation. IL-23 Bioassay Cells are also available in a Cell Propagation Model (CPM) format, as cryopreserved cells that can be thawed, propagated and banked for long-term use (IL-23 Bioassay, Propagation Model, Cat.# J3002).