4 exons.

The transcript is 1041 bp, with a 166 bp 5 untranslated region (UTR), a 570 bp coding sequence, and a 305 bp 3 UTR.

No pseudogene.

The IL23A protein (IL-23p19 subunit) is covalently linked to a p40 subunit (IL12B, IL-12p40), which is shared with IL-12, to form IL-23 (Oppmann et al., 2000). The IL23A protein requires IL12B for secretion. The receptor for IL-23 is formed by the association of a specific IL-23 receptor (IL23R) and IL-12Rbeta1 (IL12RB1), which is shared with the receptor for IL-12 (Parham et al., 2002). The receptor for IL-23 is constitutively associated with Jak2 (Janus kinase 2) and predominantly activates Stat3, with less Stat4 activation than IL-12.

The protein consists of 189 amino acids and is 20.7 kD, comprising a 19 amino acid signal peptide and a mature peptide (170 amino acids, 18.7 kD).

IL-23 is secreted by dendritic cells (DCs) and phagocytic cells activated with pathogens and pathogen-associated molecular patterns that act through toll-like receptors (TLRs) (Hunter, 2005; Kastelein et al., 2007; Goriely et al., 2008). The TLR2 ligand peptidoglycan, a cell wall component of Gram-positive bacteria, preferentially promotes the expression of IL23A but not IL12A through activation of a cytosolic receptor, nucleotide-binding oligomerization domain 2 (NOD2), with TLR2. Activation of the C-type lectins-Syc-CARD9 signaling pathway by the beta-glucan curdlan also induces IL-23 production by DCs (LeibundGut-Landmann et al., 2007). Prostaglandin E2 (PGE2) and ATP act on their G-protein-coupled receptors, EP2 and EP4 (PGE2) and P2Y (ATP), to enhance IL-23 production via an increase in cAMP concentration (Sheibanie et al., 2004; Yao et al., 2009; Schnurr et al., 2005). Lactic acid also facilitates IL-23 production (Shime et al., 2008). Although these factors themselves do not induce IL-23 production, they can shift the balance between IL-12 and IL-23 secretion by activated DCs or macrophages toward IL-23. Polarized Th1 and Th2 cells highly express IL23A mRNA but not IL12B mRNA (Oppmann et al., 2000). The roles of IL23A mRNA expression in T cells are unknown.

IL-23 receptor is mainly expressed on activated/memory T cells and natural killer (NK) cells. Monocytes, macrophage and DCs also express IL-23 receptor at low levels (Parham et al., 2002). Although IL-23 does not directly stimulate the initial differentiation of naive T cells to Th17 cells, it is essential for the full differentiation of Th17 cells and promotes their expansion and maintenance to induce IL-17A production (Korn et al., 2009). NKT cells (Rachitskaya et al., 2008) and innate lymphoid cells such as lymphoid tissue induce (LTi)-like cells (Takatori et al., 2009; Buonocore et al., 2010) express IL-23 receptor and retinoic-acid-related orphan receptor (ROR) gammat and produce IL-17 in response to IL-23. IL-1beta and IL-23 also costimulate gammadelta T cells to induce IL-17 production without T cell receptor engagement (Sutton et al., 2009).

IL23A has homology with four-helix bundle cytokine family members such as IL12A (IL-12p35), IL-6, and G-CSF. IL23A and IL12A have the highest homology, with approximately 40% of sequence identity among this family.