Novel Models to Study Stromal Cell-Leukocyte Interactions in Health and Disease

To study human immunology in general and stromal immunology in particular, it is highly motivated to move from monolayers to 3D cultures, such as organotypic models, that better mimic the function of living tissue. These models can potentially contain most if not all cell types present in tissues, in combination with different extracellular matrix components that can critically affect cell phenotype. Besides their well-established use in studies of tissue-specific cells, such as epithelial cells, endothelial cells and stromal fibroblasts in combination with extracellular components, these models have also been shown to be valuable to study how tissue participates in the regulation of leukocyte differentiation and function. Organotypic models with leukocytes represent novel powerful tools to study human stromal immunology and mechanisms involved in the regulation of leukocyte functions and inflammatory processes in human health and disease. In particular, these models are robust, long-lived and reproducible and allow monitoring of disease progression in real time, as well as the mixing of cellular constituents from healthy and pathological tissues. These models are also easy to manipulate, either genetically or by adding external stimulants, such as cytokines and pathogens, to mimic pathological conditions. It is thus not surprising that these models are proposed to be useful in toxicology screening assays, evaluating therapeutic efficacy of drugs and antibiotics, as well as in personalized medicine. Within this chapter, the most recent developments in creating organotypic models for the purpose of study of human leukocyte and stromal cell interactions, in health and disease, will be discussed, in particular focusing on live imaging. Special emphasis will be given on an organotypic model resembling human lung and its usefulness in studying the fine control of physiological and pathological processes in human health and disease. Using these models in studies on human stromal cell and leukocyte interactions will likely help identifying novel disease traits and may point out new potential targets to monitor and treat human diseases.