Abstract
To achieve immune homeostasis in such a harsh environment as the intestinal mucosa, both active and quiescent immunity operate simultaneously. Disruption of gut immune homeostasis leads to the development of intestinal immune diseases such as colitis and food allergies. Among various intestinal innate immune cells, mast cells (MCs) play critical roles in protective immunity against pathogenic microorganisms, especially at mucosal sites. This suggests the potential for a novel MC-targeting type of vaccine adjuvant. Dysregulated activation of MCs also results in inflammatory responses in mucosal compartments. The regulation of this yin and yang function of MCs remains to be elucidated. In this review, we focus on the roles of mucosal MCs in the regulation of intestinal allergic reaction, inflammation and their potential as a new target for the development of mucosal adjuvants.
Highlights
Cutaneous and mucosal compartments are continuously and directly exposed to outside environments and are the major pathogen invasion sites
Various host cells are involved in innate and acquired immunity, including innate lymphoid cells, dendritic cells (DCs) and T cells in the surface compartments. Even though these cells are generally critical for the induction of protective immunity, some of them are occasionally abnormally activated by nonpathogenic stimuli such as food allergens or endogenous ligands, and cause allergic or inflammatory diseases.[2,3]
mast cells (MCs) activation is observed in B cell-deficient mice; we have suggested the existence of multiple MC activators during intestinal inflammation.[40]
Summary
Cutaneous and mucosal compartments are continuously and directly exposed to outside environments and are the major pathogen invasion sites. MCs possess the high-affinity IgE receptor Fc epsilon receptor (FceR) on their surface; crosslinking of this receptor by an immunocomplex of the allergen-specific IgE and the allergen induces degranulation and release of histamine and effector proteases (for example, tryptase and chymase), leading to the development of allergic diseases.[6,7] MCs are divided into two types on the basis of protease expression patterns.[8] In mice, mucosal-type MCs, located in mucosal compartments, express chymase (mouse mast cell protease (mMCP)-1 and mMCP-2).[8] Connective tissue-type MCs, located in the skin and blood vessels, express chymase (for example, mMCP-4, mMCP-5), tryptase (mMCP-6 and mMCP-7) and carboxypeptidase A.8 Both MC types are involved in allergic reactions: mucosal MCs in the intestinal mucosa and connective tissue MCs in the skin or in systemic allergies.[8]. We summarize recent progress in our understanding of the molecular and cellular aspects of MC-mediated advantageous and detrimental immune responses
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