At the crossroads: mucosal immunology of the larynx

Abstract

The larynx sits at the crossroads between gastrointestinal and respiratory tracts. Besides its intrinsic importance in breathing, swallowing and voice production, the larynx is also exposed to unique immunological challenges. Given the propensity of chronic inflammatory conditions such as chronic laryngitis, which affects up to 20% of Western populations, it is surprising that our understanding of the immunology of this organ remains relatively limited. Recent work on the immunological architecture of the laryngeal mucosa, and its changes that result from external challenges and inflammatory conditions, provided valuable insight into the fascinating immunology of this organ. The lessons learnt from these investigations may go beyond devising improved therapy for chronic laryngeal inflammation. Establishing whether and how the laryngeal mucosa may be involved in the modulation of wider mucosal responses may provide novel routes to the treatment of inflammatory diseases of the respiratory and alimentary tracts such as asthma and inflammatory bowel disease.

Figure 1

The laryngeal mucosa is divided into two layers in terms of expression of antigen presenting molecules by epithelial cells: a superior, CD1d-rich layer and and deep, MHC Class1 -rich layer. We hypothesize that challenges which break down intercellular adhesion permit the presentation of incident antigens directly to the more ‘pro-inflammatory’ deeper layer, resulting in chronicity. Dendritic cells straddle the basement membrane and may orchestrate this response.

Figure 2

Immuno-fluroescence images of Reinke’s edema. (a) dense population of lamina propria by MHCII+ (green) and CD68+ (blue) cells (b) strong membranous expression of CD1d (red) by epithelial and dendritic cells, and increased CD3+CD161+ (NKT) cells in lamina propria (blue-green).

Figure 3

The laryngeal crossroads represents the junction between the sterile, IgG-dominated lower airway and the bacteria-rich, IgA-dominated upper airway. Things inhaled pass through a turbulent, narrow aperture in ‘breathing mode’ and everything ingested passes over the larynx’s surface in ‘sphincter mode’.