| pubmed-article:21076058 | pubmed:abstractText | Th17 CD4 cells are critical to inflammation. Their secretion of IL-17 drives inflammation in human diseases, including inflammatory bowel disease. Differentiation of mature Th17 cells depends on stimulation with IL-6, TGF-?, and IL-21 and the induction of ROR?t, but IL-23 is essential to Th17 phenotype, stability, and function. Induction of Th17 cells can be antagonized by IL-4 or IFN-?, but mechanisms through which terminal differentiation can be inhibited have not been identified. Human IL-23R? (HuIL23R?)-chain mRNA transcripts exist that lack exon 9 ("?9"); these are translated to a truncated receptor containing the entire external domain. This soluble variant of the HuIL23R?-chain antagonizes Th17 maturation. It is secreted and present at low levels in the blood. It represents 10% of HuIL23R?-chain mRNA, binds IL-23 in solution, and inhibits the phosphorylation of STAT3 caused by IL-23. In in vitro Th17 cell differentiation experiments, ?9 inhibits the production of the Th17-associated cytokines IL-17A and IL-17F. ?9 does not bind IL-12; thus, it is a specific inhibitor of IL-23 and a modulator of Th17 cells. Our results indicate that this soluble form of HuIL23R? likely functions to regulate Th17 activity. | lld:pubmed |
