MicroRNAs and Other Mechanisms Regulate the Expressions and Structures of Interleukin‐17 Cytokines and Receptors

Interleukin‐17 cytokines are a family of pro‐inflammatory autoimmune cytokines. Our current studies made the following findings: i) IL‐17 cytokines are not ubiquitously expressed but several receptors and ACT1 are ubiquitously expressed in tissues with a few exceptions; ii) heart and vascular tissue are in the second tier in readiness to response to IL‐17 cytokine stimulation, which require the upregulation of IL‐17 receptor components; iii) alternative transcription starting sites and alternative spliced isoforms are found in the transcripts of IL‐17 cytokines and receptors; iv) higher hypomethylation status is associated with higher expressions of IL‐17 receptors; v) the binding sites of several RNA binding proteins including an AU rich element are found in the 3'UTRs of the mRNAs of IL‐17 cytokines and receptors; and vi) numerous microRNA binding sites with the binding qualities to mRNA targets statistically equivalent to that experimentally verified microRNAs‐mRNA interaction are found in the 3'UTRs of IL‐17 cytokine and receptor mRNAs. These results suggest that several mechanisms including alternative promoters, alternative splicing, RNA binding proteins, and microRNAs regulate the structure and expression of IL‐17 cytokines and receptors. The results provide an insight into the roles of IL‐17 in mediating inflammation and immunity in cardiovascular and other tissues. This research was supported by NIH funding.