Contribution of the miRNA-interferon interaction to human disease

The type I interferon (IFN) response is the major antiviral pathway in mammals but needs to be tightly regulated to ensure effective defence against viruses whilst avoiding the negative consequences of their overproduction, resulting in autoimmune and autoinflammatory diseases.

I have recently demonstrated a central role for microRNAs (miRNAs) in maintaining optimal IFN levels, and conversely, that IFNs are important regulators of miRNA expression.

These results led me to hypothesise that there is a tight interaction between the IFN and miRNA pathways, which contributes to specific traits of human diseases where one component of this interaction is altered.

Supporting this hypothesis, our unpublished results show that diseases characterised by altered miRNA expression, such as 22q11.2DS, exhibit a dysregulated IFN response.

Vice versa, diseases characterised by an abnormal IFN response, such as systemic lupus erythematosus, display altered miRNA levels.

I aim to identify the mechanisms by which the miRNA biogenesis and IFN pathways interact and study the role of this interaction in diseases where the IFN or miRNA biogenesis pathways are altered.

These results will provide a mechanistic perspective to some of the common but unexplained traits presented in these diseases and provide novel targets for intervention strategies.