Replicating Dynamic Immune Responses at Single‐Cell Resolution within a Microfluidic Human Skin Equivalent

Abstract To enable in vitro investigation of human skin immunology, this study develops a microfluidic human skin equivalent (HSE) that supports the delivery of circulating immune cells via a vascular microchannel embedded within the dermis of a full‐thickness construct. Within this platform, activation of keratinocyte inflammation promotes monocyte migration out of the vascular channel and into the dermal and epidermal compartments. Single‐cell transcriptomic analysis reveals dynamic and cell‐specific patterns of gene expression that are characteristic of acute activation and resolution of an inflammatory immune response, and the gene signatures of the monocyte‐derived cells closely matches the differentiation trajectory of the monocytes into mature dermal macrophages. The microfluidic HSE is also applied to modeling age‐associated immune dysfunction and accurately replicates elevated monocyte recruitment in aged skin. Thus, the microfluidic HSE presented here replicates key aspects of dynamic inflammatory immune responses and represents a tractable experimental tool for interrogating mechanisms of human skin immunology.