Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
Board

Interleukin 5 plays a critical role in the expansion, differentiation and activation of the eosinophilic (and basophilic) cell type. In line with such specific role, expression of the interleukin 5 receptor alpha-subunit is restricted to eosinophils and basophils in man. In the mouse, B1-cell-specific expression is also observed. Expression levels in eosinophilic cell types appear to be determined by a combination of (i) the use of a composite promoter, and (ii) controlled alternative splicing. We have studied the latter control level in cell lines and in CD34+ cord blood progenitor cells. Alternative splicing yields transcripts from the hIL-5Ralpha gene which can either encode a signalling, membrane-anchored (IL-5Ralpha-TM) or a secreted variant with receptor antagonist activity (IL-5Ralpha-SOL). In a murine, promyelocytic FDC-P1cell line, stably transfected with a human IL-5Ralpha minigene construct, IL-5 itself, but not IL-3 or GM-CSF, can stimulate a reversible switch towards expression of the membrane-associated isoform, implying an IL-5/IL-5Ralpha-specific signalling event. Moreover, an IL-5-associated switch from predominantly soluble isoform to IL-5Ralpha-TM mRNA expression, with concomitant increase in IL-5 responsiveness, was shown during differentiation of human cord blood CD34+ cells to the eosinophilic lineage. Our results indicate ligand-dependent control of receptor expression, which may have general importance in understanding cytokine receptor regulation, and suggest a potential therapeutic intervention target.

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Presentation Number SAtavernier0544
Keywords: il-5, receptor, expression, promoter, splicing