title: Identification and characterization of multiple splice forms of the human interleukin-23 receptor alpha chain in mitogen-activated leukocytes.
abstract: The signalling of interleukin-23 (IL-23) and its receptor (IL-23R) is a key element in the differentiation of T cells to the Th17 phenotype. Here, we present the identification and characterization of human IL23R splice variants resulting from alternative splicing of the IL23R mRNA, from activated human leukocytes, following the analysis of IL23R cDNA. Twenty-four different IL23R transcripts were observed in this study, which may potentially lead to an alteration in the protein coding region of IL-23R alpha. Consequently, by analysing amino acid sequences deduced from alternatively spliced mRNA sequences, four different putative premature early termination forms of IL-23R alpha: (1) a very short 'IL-23R alpha', (2) an IL-23R alpha containing only the extracellular region, (3) a IL-23R alpha with truncated intracellular domain and (4) in-frame exon-skipping causing changes to the extracellular region of the IL-23R alpha were revealed. These changes may affect the function of IL-23R by altering the ligand-binding interaction, producing a soluble form of the receptor to act as a decoy receptor and/or modify the IL-23/IL-23R signalling, respectively. Taken together, identification of potentially functional splice variants of IL23R underscores the biological diversity of the IL23R gene and will aid in the understanding of the gene's function in normal and pathological conditions.
authors.affiliation: Genetic Immunology Laboratory, HUMIGEN LLC, The Institute for Genetic Immunology, Hamilton, NJ 08690, USA.
authors.forename: S-h
authors.initials: SH
authors.lastname: Kan
authors.forename: G
authors.initials: G
authors.lastname: Mancini
authors.forename: G
authors.initials: G
authors.lastname: Gallagher