Mast Cells in Lung Homeostasis: Beyond Type I Hypersensitivity

Abstract

Lungs are indispensable organs for the respiratory process, and maintaining their homeostasis is essential for human health and survival. However, during the lifetime of an individual, the lungs suffer countless insults that put at risk their delicate organization and function. Many cells of the immune system participate to maintain this equilibrium and to keep functional lungs. Among these cells, mast cells have recently attracted attention because of their ability to rapidly secrete many chemical and biological mediators that modulate different processes like inflammation, angiogenesis, cell proliferation, etc. In this review, we focus on recent advances in the understanding of the role that mast cells play in lung protection during infections, and of the relation of mast cell responses to type I hypersensitivity-associated pathologies. Furthermore, we discuss the potential role of mast cells during wound healing in the lung and its association with lung cancer, and how mast cells could be exploited as therapeutic targets in some diseases.

Keywords: Allergic inflammation; cancer; lungs; mast cells; pathogens; wound healing..

Fig. (1)

Pattern Recognition Receptors (PRR) expressed by mast cells. Mast cells express receptors that belong to the five main families of PRR, which allows them to directly recognize pathogens. PRR are strategically distributed within the cellular environment to detect both extracellular and intracellular pathogens. TLR: Toll-like receptor, MR: Mannose receptor, MGL: Macrophage galactose-type lectin, MINCLE: Macrophage-Inducible C-type Lectin, MAFA: Mast cell function-associated antigen, NOD: Nucleotide-binding oligomerization domain, NLRP3: NLR family, pyrin-domain containing 3, MSR: Macrophage scavenger receptor, MARCO: Macrophage receptor with collagenous structure, RIG-I: Retinoic acid inducible gene 1, MDA5: Melanoma differentiation-associated gene 5.

Fig. (2)

Functions of mast cells in the lungs. The dual role of mast cells in lung functions is depicted. White arrows indicate release of mediators that contribute to lung homeostasis. Black arrows designate liberation of mediators that contribute to pathological states in the lungs. Some mediators participate in lung homeostasis or contribute to pathology, depending on their concentration or on the timing of their production. AA: Arachidonic acid, FGF: Fibroblast Growth Factor, VEGF: Vascular Endothelial Growth Factor, TGF-β1: Transforming Growth Factor β1, BRSV: Bovine Respiratory Syncitial Virus. Arrows pointing up indicate exacerbated production.