MicroRNAs are important regulators of gene expression. We how here that one such microRNA, mir-146, regulates the expression of the atypical chemokine receptor 2 (ACKR2). ACKR2 is a pivotal regulatory of the inflammatory responses and its dysregulation has been implicated in a number of inflammatory diseases such as psoriasis. Psoriasis lesions often develop at sites of trauma or mechanical stress. Importantly, we show that mechanical stress of skin keratinocytes up-regulates mir-146 and that this is associated with a decrease in ACKR2 expression. We hypothesise that this may be one route by which inflammatory lesions develop in psoriasis.