Immunocompetent human in vitro skin models

The skin is often termed as the first line of defense against harmful agents by presenting a physical barrier and inhibiting the passage of compounds from the external environment to inside of the body. As part of its innate physiological structure, the skin contains a family of immunocompetent cells that illicit an immune response when an antigen is presented. Not only does this contribute an important role in the development and pathogenesis of a majority of skin disorders including infectious and allergic diseases, but also it provides a decisive assessment of exogenous agents that may cause harm to the host.

Although animal models have historically been used for toxicological studies, limitations with regard to ethics and their biological relevance to humans have resulted in the drive toward cell culture as an alternative technique. The first generation of these culture models has been based on “simple” mimicry of the skin relying on the growth of a single population/layer of skin-specific cells, that is, keratinocytes, melanocytes, and fibroblasts. However, recent advances in the introduction of coculture systems, 3-D architecture, and organotypic cell culture technologies have now led to the development of more robust, representative, and accurate models. This chapter aims to emphasize the development and need for more complex and sophisticated immunocompetent skin models by outlining a number of key concepts considered during their development including cell source, cell-to-cell interaction, and associated readout parameters. In addition, this chapter also includes a review of currently available in vitro and in silico immunocompetent skin models and their optimization to further understand the mechanism(s) involved in drug development and disease elucidation applications.