Fig. 1. Overview of in vitro models for mimicking cutaneous immune responses. (A) Two-dimensional co-culture systems: skin cells, immune cells, cytokines, and small molecules can be mixed and cultured together in the same culture medium. (B) Three-dimensional skin equivalents: RHE is a model of a fully differentiated epidermis without a dermal compartment; FTSE is a bi-layered skin model (epidermis and dermis). Dermis-like structures can be made from collagen gel mixed with fibroblasts, de-epidermized dermis, or self-assembled dermal sheets. Disease-associated cytokines can be added to the culture medium, and immune cells can be added inside or underneath the ECM structures. (C) Skin-on-a-chip: a microfluidic culture device that is composed of the skin and a perfusion system. Cytokines and/or immune cells can be added to the chamber of the device to reproduce inflammatory responses. RHE, reconstructed human epidermis; FTSE, full-thickness skin equivalent; ECM, extracellular matrix.