Interleukin-33 and Mast Cells Bridge Innate and Adaptive Immunity: From the Allergologist’s Perspective

Abstract

Interleukin (IL) 33, a member of the IL-1 superfamily, is an “alarmin” protein and is secreted in its active form from damaged cells undergoing necrotic cell death. Mast cells are one of the main effector cell types in allergic disorders. They secrete a variety of mediators, including T helper 2 cytokines. As mast cells have high-affinity IgE receptors (FcεRI) on their surface, they can capture circulating IgE. IgE-bound mast cells degranulate large amounts of histamine, heparin, and proteases when they encounter antigens. As IL-33 is an important mediator of innate immunity and mast cells play an important role in adaptive immune responses, interactions between the two could link innate and adaptive immunity. IL-33 promotes the adhesion of mast cells to laminin, fibronectin, and vitronectin. IL-33 increases the expression of adhesion molecules, such as intracellular adhesion molecule-1 and vascular cell adhesion molecule-1, in endothelial cells, thus enhancing mast cell adhesion to blood vessel walls. IL-33 stimulates mast cell proliferation by activating the ST2/Myd88 pathway; increases mast cell survival by the activation of survival proteins such as Bcl-XL; and promotes the growth, development, and maturation of mast cell progenitors. IL-33 is also involved in the activation of mature mast cells and production of different proinflammatory cytokines. The interaction of IL-33 and mast cells could have important clinical implications in the field of clinical urology. Epithelial dysfunction and mast cells could play an important role in the pathogenesis of interstitial cystitis. Urinary levels of IL-33 significantly increase in patients with interstitial cystitis. In addition, the number of mast cells significantly increase in the urinary bladders of patients with interstitial cystitis. Therefore, inhibition of mast cell activation and degranulation in response to increase in IL-33 is a potential therapeutic target in the treatment of interstitial cystitis.

Hormetic Effect of Chronic Hypergravity in a Mouse Model of Allergic Asthma and Rhinitis

“…This is, to our best of knowledge, quite new finding and adds to our better understanding of the pathophysiology of allergic asthma34. Also, it is quite meaningful that hypergravity could possibly be considered as an additional, non-pharmacologic treatment in the management of allergic respiratory disorders.…”

Non‐IgE mediated mast cell activation

“…IL‐33 can serve as a potent activator of MCs and has been reported to promote survival, maturation, migration, adhesion, and the production of several pro‐inflammatory cytokines (eg, IL‐4, IL‐5, IL‐6, IL‐8, and IL‐13) and chemokines (eg, MIP‐1α and MCP‐1) in these cells . In addition, in the presence of SCF, IL‐33 can also induce TNF production in MCs via a MK2/3‐, ERK1/2‐, and PI3K‐dependent pathway .…”

“…244 IL-33 can serve as a potent activator of MCs and has been reported to promote survival, maturation, migration, adhesion, and the production of several pro-inflammatory cytokines (eg, IL-4, IL-5, IL-6, IL-8, and IL-13) and chemokines (eg, MIP-1α and MCP-1) in these cells. [250][251][252][253][254][255][256][257][258][259][260] In addition, in the presence of SCF, IL-33 can also induce TNF production in MCs via a MK2/3-, ERK1/2-, and PI3K-dependent pathway. 261 Recently, Taracanova et al have shown that IL-33 and SP together amplify TNF secretion from MCs, which is mediated by the interaction of NK-1R and ST2 receptors.…”

Innate Immune Responses to Bladder Infection

“…Since mast cells lie underneath the epithelium it is unlikely that these cells make contact with bacteria or their products early in the infection. It is more likely that mast cells are activated by “danger signals” secreted by stressed or damaged epithelial cells such as ATP, IL-33 and β-defensin, all of which are potent mast cell activators (35–37). In addition to their role in initiating inflammation during infection, mast cells also appear to be important in establishing homeostasis and accelerating tissue recovery after the infection subsides.…”