Intestinal epithelium, intraepithelial lymphocytes and the gut microbiota - Key players in the pathogenesis of celiac disease

Figure 1 Schematic illustration of the intestinal barrier. The three main components of the intestinal barrier: the microbiota; epithelium, with its specialized cells (goblet cells, Paneth cells and enterocytes), together with a layer of mucus; and gut-associated lymphoid tissue cells, including IELs and dendritic cells. AJ: Adherens junction; D: Desmosome; IEL: Intraepithelial lymphocyte; TJ: Tight junction.

Figure 2 Ultrastructure and corresponding schematic representation of intercellular junctions. Transmission electron microscopy (JEOL JEM-1011, Japan; × 60000) was used to show the ultrastructure of intercellular junctions in the human small intestine. The transmission electron micrograph comes from our own research. JAM: Junction adhesion molecule.

Figure 3 Schematic illustration of celiac disease pathogenesis. Microbiota dysbiosis activates innate immunity resulting in pro-inflammatory changes, which leads to IEL infiltration and epithelial barrier disruption. This ultimately results in an increased paracellular and transcellular transfer of immunogenic gluten peptides and activation of adaptive pro-inflammatory Th1/Th17 pathways, leading to villous atrophy and production of autoantibodies against intestinal TTG2. HLA: Human leucocyte antigen; IEL: Intraepithelial lymphocyte; IL: Interleukin; INF: Interferon; NOD: Nucleotide-binding oligomerization domain; Th: T helper; TLR: Toll-like receptor; TTG2: Tissue transglutaminase 2.

Figure 4 A schematic illustration of progressive histopathological changes in the small intestine according to the modified Marsh-Oberhuber grading scale. Type 0: Normal mucosa with IEL count < 25 per 100 enterocytes; Type 1: Normal mucosa with an increased IEL count; Types 2 and 3 show increased IEL counts and lymphocytes in the lamina propria. IELs are presented as black dots. IEL: Intraepithelial lymphocyte.