A novel cytokine receptor-ligand pair - Identification, molecular characterization, and in vivo immunomodulatory activity

As part of a large scale effort to discover novel secreted proteins, a cDNA encoding a novel cytokine was identified. Alignments of the sequence of th e new protein, designated IL-17B, suggest it to be a homolog of the recentl y described T cell-derived cytokine, IL-17. By Northern analysis, EST distr ibution and real-time quantitative polymerase chain reaction analysis, mRNA was detected in many cell types. A novel type I transmembrane protein, ide ntified in an EST data base by homology to IL-17R, was found to bind specif ically IL-17B, as determined by surface plasmon resonance analysis, flow cy tometry, and co-immunoprecipitation experiments. Readily detectable transcr iption of IL-17BR was restricted to human kidney, pancreas, liver, brain, a nd intestines and only a few of the many cell lines tested. By using. a rod ent ortholog of IL-17BR as a probe, IL-17BR message was found to be drastic ally up-regulated during intestinal inflammation elicited by indomethacin t reatment in rats. In addition, intraperitoneal injection of IL-17B purified from Chinese hamster ovary cells caused marked neutrophil migration in nor mal mice, in a specific and dose-dependent manner. Together these results s uggest that IL-17B may be a novel proinflammatory cytokine acting on a rest ricted set of target cell types. They also demonstrate the strength of geno mic approaches in the unraveling of novel biological pathways.