Interleukin 23
Interleukin 23 (IL-23) is a heterodimeric cytokine composed of an IL-12B (IL-12p40) subunit (which is shared with IL-12) and an IL-23A (IL-23p19) subunit. IL-23 is part of the IL-12 family of cytokines. The functional receptor for IL-23 (the IL-23 receptor) consists of a heterodimer between IL-12Rβ1 and IL-23R. IL-23 was first described by Robert Kastelein and colleagues at the DNAX research institute using a combination of computational, biochemical and cellular immunology approaches. IL-23 is an inflammatory cytokine. It has been shown to be a key cytokine for T helper type 17 cell (Th17 cell) maintenance and expansion. Polarisation to a Th17 phenotype is triggered by IL-6 and TGF-β, which activate the Th17 transcription factor RORγt. IL-23 stabilises RORγt and thus enables Th17 cells to release their effector cytokines, such as IL-17, IL-21, IL-22 and GM-CSF, which mediate protection against extracellular fungi and bacteria and participate in barrier immunity. Effects similar to those IL-23 has on Th17 cells were described for type 3 innate lymphoid cells, which actively secrete Th17 cytokines upon IL-23 stimulation. Natural killer cells also express the IL-23 receptor. They respond with increased interferon-γ secretion and enhanced antibody-dependent cellular cytotoxicity. IL-23 also induces proliferation of CD4 memory T cells (but not naïve T cells). Besides its proinflammatory effects, IL-23 promotes angiogenesis. IL-23 is mainly secreted by activated dendritic cells, macrophages or monocytes. Innate lymphoid cells and γδ T cells also produce IL-23. B cells produce IL-23 through B cell antigen receptor signaling. Secretion is stimulated by an antigen stimulus recognised by a pattern recognition receptor. IL-23 imbalance and increase is associated with autoimmune diseases and cancer. It is thus a target for therapeutic research. IL-23 expression by dendritic cells is further induced by thymic stromal lymphopoietin, a proallergic cytokine expressed by keratinocytes that is elevated in psoriatic lesions.