Interna tional Neurourology Journal 2015;19: Interleukin-33 and Mast Cells Bridge Innate and Adaptive Immunity: From the Allergologist’s Perspective Tae Young Jang, Young Hyo Kim Department of Otorhinolaryngology-Head and Neck Surgery, Inha University School of Medicine, Incheon, Korea This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Interna tional Neurourology Journal 2015;19: 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.

Interna tional Neurourology Journal 2015;19: 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.

Interna tional Neurourology Journal 2015;19: 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.

Interna tional Neurourology Journal 2015;19: ProcessEffects reported in the literature AdhesionPromotes adhesion to laminin, fibronectin, and vitronectin [51] Promotes SCF-mediated adhesion of mast cells to fibronectin [13] Increases expression of adhesion molecules, such as ICAM-1 and VCAM-1, in endothelial cells [54] ProliferationEnhances proliferation of mast cells through activation of the ST2/Myd88 pathway [55] SurvivalActivates survival proteins such as Bcl-XL [56] Growth, development, and maturationPromotes maturation of CD34+ progenitor cells to tryptase-producing cells [57] Promotes maturation of mast cell progenitors in vitro [57] ActivationPromotes production of Th2 cytokines and chemokines, prostaglandins, and leukotrienes [57–59] Promotes autoantibody-mediated degranulation of mast cells in synovial tissue [60] Production of cytokines and chemokinesPromotes production of IL-4, IL-6, IL-13, TNF-a, and GM-CSF, and chemokines MIP-2 (CXCL2), KC (CXCL1), MCP-1 (CCL2), MIP-1a (CCL3), an d MCP-3 (CCL7) [58,62-64,66] Table. 1. Effects of IL-33 on the adhesion, proliferation, survival, development, and activation of mast cells in allergic inflammation IL, interleukin; ICAM, intracellular adhesion molecule; VCAM, vascular cell adhesion molecule; Th2, T helper 2; TNF, tumor necrosis factor; GM-CSF, granulocyte macrophage-colony stimulating factor; MIP, macrophage inflammatory protein; KC, keratinocyte chemoattractant; MCP, monocyte chemoattractant protein.