MiRNA-mediated regulation of epithelial homeostasis and immune responses

Epithelial cells are important components of both the physical barrier and the innate immune system, in the skin and other epithelial surfaces.

Many immune-mediated skin diseases, including atopic dermatitis (AD) and psoriasis, are characterized by activation of the skin’s epithelial cells, keratinocytes, and barrier dysfunction.

MicroRNAs (miRNAs) are short non-coding RNAs, that regulate gene expression, development, diseases and inflammatory programs.

Previously, we identified the miRNA called miR-149 as a surprisingly powerful regulator of keratinocyte inflammatory responses.

The overarching aim of this project is to delineate the function of this important but as yet relatively poorly characterized miRNA in epithelial homeostasis and immunity.We have generated mice with keratinocyte-specific deletion of miR-149, which will be extensively and systematically tested in a series of models of epidermal barrier formation, several models of inflammatory skin conditions, inflammatory memory and ageing.

These studies will be complemented with functional studies of miR-149 in 3D epidermal equivalents constructed from human cells, and with studies on human skin samples from inflammatory and infectious diseases.This project will provide unprecedented insights into miRNA-mediated regulation in epithelial homeostasis and immunity, and will pave the way towards future RNA-based medicines for inflammatory and infectious diseases.