Fig. 1. IL-23 is a biologically active cytokine composed of two subunits: p19 and the p40 subunit of IL-12 (panel A). IL-23 binds specifically to the IL-12 R beta 1 subunit and can stimulate IFN-gamma production and proliferation in PHA blast T cells and activated CD45RO (memory) T cells (panel B).
p19 is a novel four-alpha helix cytokine that is most closely related in structure to the p35 subunit of IL-12 (IL-12 p35).1 p19 alone has no determined biological activity, but combines with the p40 subunit of IL-12 (IL-12 p40) to form a biologically active composite cytokine called IL-23 (see Figure 1). Activated human and mouse dendritic cells secrete the p19/p40 heterodimer. The functional high affinity IL-12 receptor is composed of at least two beta-type receptor subunits (IL-12 R beta 1 and IL-12 R beta 2), each independently having low affinity for IL-12. IL-12 p35 interacts primarily with IL-12 R beta 2, while IL-12 p40 interacts primarily with IL-12 R beta 1. Thus, it is not surprising that IL-23 engages IL-12 R beta 1, but fails to bind to the IL-12 R beta 2. The observation that IL-23 activates STAT4, a signaling activity mediated by IL-12 R beta 2 and not by IL-12 R beta 1, predicts that IL-23 signaling requires a yet unidentified receptor subunit in addition to IL-12 R beta 1. IL-23 has biological activities that are similar to IL-12, but also distinct. In contrast to IL-12, IL-23 is a strong inducer of memory (CD4+CD45RB low) T cell proliferation. Similar to IL-12, IL-23 stimulates IFN-gamma production and proliferation in PHA blast T cells and in activated CD45RO (memory) T cells.