Immune Homeostasis in Epithelial Cells: Evidence and Role of Inflammasome Signaling Reviewed

Abstract

The epithelium regulates the interaction between the noxious xenogenous, as well as the microbial environment and the immune system, not only by providing a barrier but also by expressing a number of immunoregulatory membrane receptors, and intracellular danger sensors and their downstream effectors. Amongst these are a number of inflammasome sensor subtypes, which have been initially characterized in myeloid cells and described to be activated upon assembly into multiprotein complexes by microbial and environmental triggers. This review compiles a vast amount of literature that supports a pivotal role for inflammasomes in the various epithelial barriers of the human body as essential factors maintaining immune signaling and homeostasis.

Figure 1

Schematic representation of all intracellular nucleotide-binding oligomerization domain receptors, in short NOD-like receptor (NLR), and pyrin and HIN200 domain-containing (PYHIN) inflammasome members, which are each able to assemble with the protease caspase-1 via the adaptor molecule apoptosis-associated speck-like protein containing a CARD (ASC) when triggered. This allows the activated enzyme to cleave and mature proinflammatory cytokines, interleukin- (IL-) 1β, and IL-18 as well as inducing the unconventional release of basic fibroblast growth factor (bFGF) and high-mobility group box 1 (HMGB1).

Figure 2

Schematic representation of stratified squamous epithelium of the skin and oral mucosa. Toxic molecules and environmental and cellular stressors as well as microbial antigens can individually activate one or more inflammasome subtypes, leading to caspase-1 activation and the release of IL-1β, IL-18, bFGF, and HMGB1.

Figure 3

Schematic representations of simple columnar epithelial cells lining the digestive tract reflecting multiple inflammasomes that are described to be activated by different described agents AIM2, IFI16, MNDA, and PYHIN1 are subtypes of the non-NLR inflammasome family.

Figure 4

Schematic representation of pseudostratified columnar epithelium of the lung indicating a variety of environmental and microbial molecules that is able to activate the inflammasome with a subsequent release of cytokines, alarmins, and growth factors.

Figure 5

Schematic representations of simple cuboidal epithelial cells lining the urogenital tract in which different inflammasomes have been described to be activated by independent instigators triggering the release of inflammasome readouts.