Gastrointestinal epithelial innate immunity-regionalization and organoids as new model

J Mol Med (Berl). 2021 Apr;99(4):517-530. doi: 10.1007/s00109-021-02043-9. Epub 2021 Feb 4.

Abstract

The human gastrointestinal tract is in constant contact with microbial stimuli. Its barriers have to ensure co-existence with the commensal bacteria, while enabling surveillance of intruding pathogens. At the centre of the interaction lies the epithelial layer, which marks the boundaries of the body. It is equipped with a multitude of different innate immune sensors, such as Toll-like receptors, to mount inflammatory responses to microbes. Dysfunction of this intricate system results in inflammation-associated pathologies, such as inflammatory bowel disease. However, the complexity of the cellular interactions, their molecular basis and their development remains poorly understood. In recent years, stem cell-derived organoids have gained increasing attention as promising models for both development and a broad range of pathologies, including infectious diseases. In addition, organoids enable the study of epithelial innate immunity in vitro. In this review, we focus on the gastrointestinal epithelial barrier and its regional organization to discuss innate immune sensing and development.

Keywords: Gastrointestinal tract; Immunity; Regionalization and organoids.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Animals
  • Biological Specimen Banks
  • Cell Polarity
  • Epithelial Cells / immunology*
  • Forecasting
  • Gastrointestinal Microbiome / immunology
  • Gastrointestinal Tract / cytology
  • Gastrointestinal Tract / immunology*
  • Gastrointestinal Tract / metabolism
  • Gastrointestinal Tract / microbiology
  • Gene Expression Profiling
  • Goblet Cells / immunology
  • Humans
  • Immune Tolerance
  • Immunity, Innate*
  • Infant, Newborn
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / pathology
  • Intestinal Mucosa / immunology
  • Mice
  • Models, Immunological
  • NF-kappa B / physiology
  • Organ Specificity
  • Organoids* / cytology
  • Organoids* / immunology
  • Paneth Cells / immunology
  • Peyer's Patches / immunology
  • Stem Cells / immunology
  • Toll-Like Receptors / immunology

Substances

  • NF-kappa B
  • Toll-Like Receptors