Novel IL-15 isoforms generated by alternative splicing are expressed in the intestinal epithelium

Previous studies have identified mRNA three isoforms encoding interleukin-15 (IL-15) that are produced through differential splicing and encode for the same mature IL-15 protein with two different signal peptides. Our analysis of mouse intestinal epithelial cells revealed two new IL-15 mRNA isoforms generated by different alternative splicing events. In one form (IL-15 Delta E6), exon 6 is absent, and in the second form the first 48 nt of exon 7 are absent (IL-15 Delta E7) through usage of an alternative 50 splicing site within exon 7. These mRNA isoforms encoded in-frame IL-15 protein variants lacking either 15aa (IL-15 Delta E6) or 16aa (IL-15 Delta E7) both utilizing the normal long signal peptide. Significant structural changes were predicted for these new IL- 15 isoforms. RNAse protection assays revealed the highest expression of isoform mRNA in the intestinal epithelium and functional analysis of recombinant IL-15 isoform proteins suggested possible regulatory functions.