A Novel Cytokine Receptor-Ligand Pair

Abstract

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 the new protein, designated IL-17B, suggest it to be a homolog of the recently described T cell-derived cytokine, IL-17. By Northern analysis, EST distribution and real-time quantitative polymerase chain reaction analysis, mRNA was detected in many cell types. A novel type I transmembrane protein, identified in an EST data base by homology to IL-17R, was found to bind specifically IL-17B, as determined by surface plasmon resonance analysis, flow cytometry, and co-immunoprecipitation experiments. Readily detectable transcription of IL-17BR was restricted to human kidney, pancreas, liver, brain, and intestines and only a few of the many cell lines tested. By using a rodent ortholog of IL-17BR as a probe, IL-17BR message was found to be drastically up-regulated during intestinal inflammation elicited by indomethacin treatment in rats. In addition, intraperitoneal injection of IL-17B purified from Chinese hamster ovary cells caused marked neutrophil migration in normal mice, in a specific and dose-dependent manner. Together these results suggest that IL-17B may be a novel proinflammatory cytokine acting on a restricted set of target cell types. They also demonstrate the strength of genomic approaches in the unraveling of novel biological pathways.

Exploring the two-gene ratio in breast cancer—independent roles for HOXB13 and IL17BR in prediction of clinical outcome

“…The protein is a cytokine receptor that specifically binds to IL17B and IL17E in the IL17 family [29,30]. One may speculate that IL17BR could act in a protective way by taking part in the immune response against cancer cells, but this remains to be shown.…”

Interleukins and interleukin receptors in rheumatoid arthritis: Research, diagnostics and clinical implications

“…IL-17A was the first member and the others were discovered shortly after the first one by large-scale sequencing of the human genome [123][124][125][126] . Members of this family share the highest amino acid sequence homology and perform distinct biological functions [127] .…”

Transgenic overexpression of human IL-17E results in eosinophilia, B-lymphocyte hyperplasia, and altered antibody production

“…Four new family members have been identified, namely, IL-17B, IL-17C, IL-17E/IL-25, and IL-17F. [20][21][22][23][24][25] These molecules possess approximately 25% to 30% homology to IL-17, consist of 155 to 197 amino acids with a molecular mass of 20 to 30 kDa, and bind to specific cognate IL-17 receptors with little cross-reactivity. To date, 2 IL-17 receptors have been identified, IL-17R, which binds IL-17, and IL-17Rh1 (IL-17BR/Evi27), which binds both IL-17B and IL-17E.…”