Interleukin-5 does not influence differential transcription of transmembrane and soluble isoforms of IL-5Ra in vivo

Interleukin-5 (IL-5) promotes signal transduction and expansion of eosinophil colonies in bone marrow via interactions with its heterodimeric receptor (IL-5R). Two variants encoding soluble forms of the alpha subunit (sIL-5Ra) have been described, although the signals promoting and/or limiting differential transcription remain to be clarified. Objectives: Our intent was to explore the role of IL-5 in regulating differential transcription of these splice variants in vivo. Methods: We have designed a quantitative reverse transcriptase-polymerase chain reaction assay to detect transcripts encoding the transmembrane, soluble 1 and 2 forms of IL-5Ra in two strains of wild-type (BALB/c and C57BL/6) and corresponding IL-5 gene-deleted mice. Wild-type mice respond to S. mansoni infection with a gradual increase in serum IL-5 and eosinophilia, which is not observed in IL-5 gene-deleted mice. Results and conclusions: We find that IL-5 is not necessary for differential splicing to occur in vivo, as all three forms of the IL-5Ra are detected in both strains of IL-5 gene-deleted mice, with ratios of transcript expression (transmembrane : soluble 1 : soluble 2) that were indistinguishable from their wild-type counterparts. Differential splicing does vary markedly between strains, potentially because of local effects of strain-specific polymorphisms.