Int Neurourol J.  2015 Sep;19(3):142-150. 10.5213/inj.2015.19.3.142.

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

• Jang TY
• Kim YH

• KMID: 2380842
• DOI: http://doi.org/10.5213/inj.2015.19.3.142

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 (FcepsilonRI) 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.

Keyword

Interleukin-33, Mouse; Mast Cells; Cystitis, Interstitial; Allergy and Immunology

MeSH Terms

Adaptive Immunity*
Allergy and Immunology
Blood Vessels
Cell Death
Cystitis, Interstitial
Cytokines
Endothelial Cells
Fibronectins
Heparin
Histamine
Humans
Immunity, Innate
Immunoglobulin E
Interleukin-1
Interleukins
Laminin
Mast Cells*
Peptide Hydrolases
Receptors, IgE
Urinary Bladder
Urology
Vascular Cell Adhesion Molecule-1
Vitronectin
Cytokines
Fibronectins
Heparin
Histamine
Immunoglobulin E
Interleukin-1
Interleukins
Laminin
Peptide Hydrolases
Receptors, IgE
Vascular Cell Adhesion Molecule-1
Vitronectin