Understanding the expression of IL15 and IL15Rα Splice variants in Celiac Disease

Abstract

Celiac disease (CD) is an autoimmune disease of the small intestine. Different factors such as dietary components, genetics, immune response, and loss of intestinal permeability work in concert to contribute to the pathogenesis of CD. In CD the cytokine IL15, pleotropic cytokine reported to participate in many facets of the immune system, and its receptor alpha (IL15Rα) have been reported to be upregulated. IL15 is regulated at multiple distinct levels of transcription, translation, intracellular trafficking and also by its receptor. Disturbance in any of these regulatory mechanisms may lead to a dysregulated IL15 production. Understanding the complex machinery of the IL15/IL15Rα system will thus help us to better understand its role in the pathogenesis of CD. Quantitative real time PCR (QRTPCR) was used to investigate if the upregulated IL15 and IL15 receptor alpha reported in CD is a consequence of differential exon expression. Peripheral blood mononuclear cells (PBMCs) from patient and control samples were used to carryout QRT PCR on IL15 and IL15Rα mRNA to investigate their exon expression profile. We found a clear and significant difference in expression of IL15 mRNA and saw differential expression of specific exons in IL15Rα mRNA in PBMC from the control and patient groups. We also report that the major immune cell subset responsible for the cytokine and its receptor alpha mRNA are the monocytes. Overall this is a good pilot study with some interesting findings, which with further investigations can help give a better insight to disease pathogenesis. We believe that future studies on these reports may assist in establishing IL15 and its receptor isoforms as a novel biomarkers for CD.