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背景
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Interleukin 23 (IL-23) is a heterodimeric cytokine composed of two disulfide-linked subunits, a p19 subunit that is unique to IL-23, and a p40 subunit that is shared with IL-12. The p19 subunit has homology to the p35 subunit of IL-12, as well as to other single chain cytokines such as IL-6 and IL-11. The p40 subunit is homologous to the extracellular domains of the hematopoietic cytokine receptors. The rat p19 cDNA encodes a 196 amino acid (aa) residue precursor protein with a putative 19 aa signal peptide and 177 aa mature protein. The mature rat p19 protein shares 88%, 78%, 76%, 75%, 71%, and 70% aa sequence identity with mouse, human, canine, equine, guinea pig, and bovine, respectively. Activated macrophages and dendritic cells express p19 and p40 concurrently to produce IL-23. The functional IL-23 receptor complex consists of two receptor subunits, the IL-12 receptor beta 1 subunit (IL-12R beta 1) and the IL-23-specific receptor subunit (IL-23R). IL-23 and IL-12 have overlapping but distinct biological activities. IL-12 drives development of Th1 cells and induces production of IFN-gamma by NK cells; IL-23 induces proliferation of Th17 cells and CD4+ memory T cells distinct from Th1 which produce IL-17, a potent proinflammatory cytokine. IL-23 also drives IL-17 production by NK cells and neutrophils. While both IL-12 and IL-23 pathways respond to infectious agents, the IL-23 - IL-17 immune pathway induces the earliest recruitment of neutrophils to the site of infection while the more classic host defense and cytotoxic response is stimulated by IL-12. Dysregulation of the IL-23 - IL-17 immune pathway has a key role in organ-specific autoimmune inflammatory tissue destruction.
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