Two Sides of the Coin: Mast Cells as a Key Regulator of Allergy and Acute/Chronic Inflammation

Abstract

It is well known that mast cells (MCs) initiate type I allergic reactions and inflammation in a quick response to the various stimulants, including—but not limited to—allergens, pathogen-associated molecular patterns (PAMPs), and damage-associated molecular patterns (DAMPs). MCs highly express receptors of these ligands and proteases (e.g., tryptase, chymase) and cytokines (TNF), and other granular components (e.g., histamine and serotonin) and aggravate the allergic reaction and inflammation. On the other hand, accumulated evidence has revealed that MCs also possess immune-regulatory functions, suppressing chronic inflammation and allergic reactions on some occasions. IL-2 and IL-10 released from MCs inhibit excessive immune responses. Recently, it has been revealed that allergen immunotherapy modulates the function of MCs from their allergic function to their regulatory function to suppress allergic reactions. This evidence suggests the possibility that manipulation of MCs functions will result in a novel approach to the treatment of various MCs-mediated diseases.

Association of Food Allergy, Respiratory Allergy, and Skin Allergy with Attention Deficit/Hyperactivity Disorder among Children

“…Food-induced microbiome changes and allergic immune activation are thought to affect brain function through neuroimmune interactions, which can affect the enteric nervous system and central nervous system and eventually lead to neurodevelopmental abnormalities [ 44 ]. Fourth, inflammatory cytokines produced in allergic conditions could lead to altered metabolism of norepinephrine and dopamine, which was considered a critical neurological change in ADHD pathology [ 36 , 45 ]. Lastly, it is also possible that there is a shared cause leading to both allergic conditions and ADHD or a bidirectional association between allergic conditions and ADHD.…”

Mucosal Mast Cells as Key Effector Cells in Food Allergies

“…Although IL-10 is a well-known immunosuppressive cytokine produced by Tregs, it also plays an important role in the differentiation and functional capacity of Tregs themselves [102,103]. Takasato et al [104,105] have demonstrated a helpful effect of MMCs in OIT using a mouse model of OIT. OIT shifted MMCs from pathogenic (or pro-allergic) status to regulatory (desensitization) status.…”

Mast Cells in the Mammalian Testis and Epididymis—Animal Models and Detection Methods

“…MCs influence inflammation, fibrosis, the gastrointestinal and reproductive tracts, hemostasis, the and cardiovascular system [ 17 ], and their disturbances are classified as secondary MC disorders, often influenced by interleukin (IL)-3, IL-4, IL-9, IL-10, IL-33, TGF-β, SCF and many other agents ( Figure 1 ) [ 21 ]. In recent years, significantly more is known about their regulatory, physiological function, such as wound healing, immune tolerance, and suppression of allergies, and not just their pathological involvement [ 3 ].…”

“…The IgE-dependent pathway is considered as the main one for MC physiological activation in host defense against parasitic infections and the initiation of type I allergic reactions [ 23 ] and requires sensitization to an allergen. On the other hand, IgE-independent pathways have also been proven to serve pivotal roles in the pathophysiology of allergic and pseudoallergic responses but include MC activation by inflammatory mediators, complement fragments, cytokines, and neuropeptide substance P through specific G-protein-coupled receptors (GPCR) [ 3 ].…”

“…Mast cells (MCs) have a crucial role in promoting hypersensitivity reactions and reactions to parasitic diseases. They are essential in developing autoimmune diseases, promoting acute and chronic inflammatory responses [ 1 , 2 ], and recognized as critical regulators of immune modulation, capable of suppressing allergic reactions and chronic inflammation [ 3 ]. Mast cell precursor population originates at the yolk sac [ 4 ], while in adult tissues, MC precursors reside in the bone marrow and migrate to tissues where they further differentiate and serve as sentinel cells under the influence of intrinsic and external stimuli [ 5 ].…”