Extract

Historically, immunological research, especially when involving human cells, has relied heavily on the use of in vitro cultures. While this has led to countless discoveries, in vitro cultures tend to lack physiological structure and cellular diversity, which limits their ability to recapitulate in vivo tissue. This barrier has been bridged by advances in stem cell research that led to development of organoids, i.e. self-assembling 3D tissue cultures whose cell composition, structure, and functions resemble the tissue/organ of origin, which currently can be established from a constantly increasing list of tissues and organs [1]. Intestinal organoids were some of the first organoids to be developed, with a single stem cell from murine small-intestinal crypts being shown to support formation of organoids with the architecture of intestinal crypts and presence of multiple epithelial cell types [2]. Subsequent studies derived intestinal organoids from human intestinal crypts [3] and from human-induced pluripotent cells, with the last ones containing mesenchymal cells in addition to epithelial cells [4, 5]. Given the experimental flexibility of gut organoids, coupled with the continuous emergence of studies documenting the close interactions between immune, microbiota, and epithelial cells in the gut [6], these 3D cultures caught the attention of mucosal immunologists as a powerful system enabling the detailed study of these cellular interactions in the intestine and their importance in health and disease. Organoid research, which was initially focused on stem cell and tissue development, has therefore since been adopted and adapted by immunologists that have been recognizing the advantages of using these models for their studies. That is the main focus of this review series, which covers the use of intestinal organoid models in different aspects of immunological research.

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