IL‑17 Secretion Induced by|
IL‑23 and Neutralization by Mouse IL‑23 R Antibody. In the presence of Recombinant Mouse IL‑2 (10 ng/mL, Catalog # 402-ML), Recombinant Mouse IL‑23 (Catalog # 1887-ML) stimulates IL‑17 secretion in mouse splenocytes in a dose-dependent manner (orange line), as measured by the Mouse IL‑17 Quantikine ELISA Kit (Catalog # M1700). Under these conditions, IL‑17 secretion elicited by Recombinant Mouse IL‑23 (0.75 ng/mL) is neutralized (green line) by increasing concentrations of Mouse IL‑23 R Monoclonal Antibody (Catalog # MAB1686). The ND50 is typically 0.1-0.4 µg/mL.
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 (1‑5). The functional IL-23 receptor complex consists of two receptor subunits, the IL-12 receptor beta 1 subunit (IL-12 R beta 1) and the IL-23-specific receptor subunit (IL-23 R) (3). Mouse IL-23 R cDNA encodes a 644 amino acid (aa) type I transmembrane protein with a 23 aa residue signal peptide, a 349 aa residue extracellular domain, a 23 aa residue transmembrane domain and a 249 aa residue cytoplasmic region. IL-23 R shares structural features with the IL-12 R beta 2, including an N-terminal Ig-like domain, two cytokine receptor domains and multiple glycosylation sites in the extracellular domain. IL-23 R lacks the three extracellular membrane-proximal fibronectin-type III domains present on IL-12 R beta 2. IL-23 R has a WQPWS sequence in the transmembrane-proximal cytokine receptor domain similar to the cytokine receptor signature WSXWS motif. The cytoplasmic region of IL-23 R has three potential Src homology 2 domain-binding sites and two potential Stat-binding sites. The gene for human IL-23 R is located on human chromosome 1 within 150 kb of IL-12 R beta 2. Human and mouse IL-23 R share 66% amino acid sequence identity. Mouse IL-23 R is expressed in mouse Th1 and Th2 cells, bone marrow, dendritic cells and macrophages. It is also expressed by mouse CD4+ CD45RBlow memory T cells but at much lower levels by mouse CD4+ CD45RBhigh cells. IL-23 initiates a signal transduction cascade similar to that of IL-12 and involves Jak2, Tyk2, STAT1, STAT3, STAT4, and STAT5. IL-23 has biological activities that are similar to, but distinct from, IL-12.
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