A novel intestinal organoid-based in vitro co-culture system to dissect out the initial host defense system

Excerpt

The surface of intestine in adult humans, which spans an area of approximately 200–400 m² as big as the area of tennis court [1], provides the first physiological defense against intestinal luminal contents, including a huge variety of microorganisms and food antigens [2]. The intraepithelial lymphocytes (IELs), which reside within the epithelium, contribute to restoring the integrity of the epithelial barrier to maintain the initial host defense against enteric microorganisms. In contrast, IELs can also damage epithelial cells and induce inflammatory responses through their cytotoxic activity and production of inflammatory cytokines such as IFN-γ [3, 4]. IELs are characterized by extremely heterogeneous T cell populations, which are classified into “induced IELs”, which develop through thymic selection and increase with age, and “natural IELs”, which contain at least two unique T cell subsets that recognize self-antigens and non-peptide antigens [3, 4]. One subset in natural IELs expresses CD8αα homodimers and develops through “alternative positive selection”. Another subset, which expresses T cell receptor (TCR) γδ, develops extrathymically, presents at birth, and decreases with age. However, the origin, development pathways, and functions of natural IELs have been under long-standing debates [3, 4]. …