Control of local immunity by airway epithelial cells

Abstract

The lung is ventilated by thousand liters of air per day. Inevitably, the respiratory system comes into contact with airborne microbial compounds, most of them harmless contaminants. Airway epithelial cells are known to have innate sensor functions, thus being able to detect microbial danger. To avoid chronic inflammation, the pulmonary system has developed specific means to control local immune responses. Even though airway epithelial cells can act as proinflammatory promoters, we propose that under homeostatic conditions airway epithelial cells are important modulators of immune responses in the lung. In this review, we discuss epithelial cell regulatory functions that control reactivity of professional immune cells within the microenvironment of the airways and how these mechanisms are altered in pulmonary diseases. Regulation by epithelial cells can be divided into two mechanisms: (1) mediators regulate epithelial cells' innate sensitivity in cis and (2) factors are produced that limit reactivity of immune cells in trans.

Immune-mediated inflammation in the pathogenesis of emphysema: insights from mouse models

“…It has become abundantly clear that the epithelial cells that line the conducting and respiratory airways are not simply passive barriers to limit access to chemical and biological exposures, but vital local sensors that communicate the level of danger (Weitnauer, et al, 2016). The major cell types that form the peudostratified cell layer of the conducting airways include ciliated epithelial cells, mucus-producing goblet cells, non-ciliated secretory club cells (formally termed Clara cells) and multipotent basal cells.…”

“…Deployment of CD200, PD-L1, αvβ6 integrin and E-cadherin on their baso-lateral membrane modulates the activation of mononuclear cells and lymphocytes (Weitnauer, Mijosek and Dalpke, 2016). Cytokines, such as IL-33, IL-25 and TSLP, and stimulatory molecules such as arachidonic acid metabolites are released locally from epithelial cells and can have an effect on the nature, intensity and duration of immune activation (Hasenberg, Stegemann-Koniszewski and Gunzer, 2013, Pouwels, et al, 2014, Tolle and Standiford, 2013, Weitnauer, Mijosek and Dalpke, 2016). …”

Negative Regulation of Type 2 Immunity

“…This notion has been supported by numerous studies that portray epithelium as limiting inflammation during homeostasis [65, 66]. This function of epithelium is logical when placed in context: in the gastrointestinal and respiratory tracts, single-layer epithelium must maintain barrier integrity while allowing efficient transfer of necessary nutrients and gases.…”

Par3 integrates Tiam1 and phosphatidylinositol 3-kinase signaling to change apical membrane identity

“…The mucosal barrier, composed of polarized epithelial cells with distinct apical and basolateral membranes, represents the first line of defense against most microbes (Weitnauer et al , 2016). Understanding how successful pathogens overcome this barrier may provide unique insights into how cell polarity is established and maintained, as well as shed light on other disease processes such as cancer metastasis and tissue repair (Ruch and Engel, 2017).…”