Identification of a soluble isoform of human IL-17RA generated by alternative splicing

• An alternative splice variant of human IL-17RA was identified at the mRNA level.
• The variant encodes an isoform of IL-17RA lacking the transmembrane region.
• Soluble IL-17RA protein was detected in human cell culture media.

IL-17RA, a member of the interleukin (IL)-17 receptor family, is a single membrane-spanning protein that ubiquitously expressed on the cell surface. IL-17RA transduces IL-17A, IL-17F, and IL-17A/F heterodimer-mediated signals by forming a complex with IL-17RC, and also signals the IL-17E (also known as IL-25) response in combination with IL-17RB (also known as IL-25R). Previously, soluble isoforms of human IL-17RC and IL-17RB have been reported, but the existence of a soluble isoform of human IL-17RA has remained unclear. Here, we report the identification of a soluble isoform of human IL-17RA at the mRNA and protein levels. Reverse transcribed PCR experiments showed that the IL-17RA variant is generated by spliced out of exon 11 encoding the transmembrane region in a variety of human tissues. The soluble IL-17RA isoform was detected in the culture media of human cell lines by Western blotting. The existence of the soluble IL-17RA isoform sheds new light on the regulation of IL-17RA mediated responses.