Contributions of intestinal epithelial barriers to health and disease

Abstract

A core function of epithelia is to form barriers that separate tissue compartments within complex organisms. These barriers also separate the internal milieu from the external environment and are, therefore, an essential component of host defense. However, in many cases, a perfect barrier would be improbable with life itself. Examples include the air spaces within the lungs, the renal tubules, and the intestines. Here, we focus on the mechanisms by which barriers are assembled, maintained, and regulated in the context of health and disease. Because of its unique challenges and extensive study, we focus on the gastrointestinal tract as an organ-specific example of the essential contributions of the paracellular barrier to life.

Fig. 1. Cell-cell adhesion in the intestinal epithelia

(A) Transmission electron micrograph (TEM) image of intestinal epithelial cells. Microvilli (Mv), tight junction (TJ), adherens junction (AJ), and desmosomes (D). (B) Freeze-fracture electron micrograph image of intestinal epithelial cells. Noted the thin tight junction strands below the microvilli. (C) Localization and molecular components of tight junction, adherens junction, and desomosomes. (D) Mechanism by which cytokines increase pore and leak pathway permeability. Apoptosis is shown as a cause of increased unrestricted pathway flux.

Fig. 2. Differential expression of claudins during development in human intestine

Expression pattern of human claudin-2 and -15 in the villus and crypt of duodenum biopsy from a female child (3-yr old) or female adult (80-yr old). Note that claudin-15 is a dominant Na+ channel tight junction protein in the villus of child. Scale bar=0.1 mm (low magnification images), 20 μm (insets).