IL‐33: biological properties, functions, and roles in airway disease

Abstract

Summary Interleukin (IL)-33 is a key cytokine involved in type 2 immunity and allergic airway diseases. Abundantly expressed in lung epithelial cells, IL-33 plays critical roles in both innate and adaptive immune responses in mucosal organs. In innate immunity, IL-33 and group 2 innate lymphoid cells (ILC2s) provide an essential axis for rapid immune responses and tissue homeostasis. In adaptive immunity, IL-33 interacts with dendritic cells, Th2 cells, follicular T cells, and regulatory T cells, where IL-33 influences the development of chronic airway inflammation and tissue remodeling. The clinical findings that both the IL-33 and ILC2 levels are elevated in patients with allergic airway diseases suggest that IL-33 plays an important role in the pathogenesis of these diseases. IL-33 and ILC2 may also serve as biomarkers for disease classification and to monitor the progression of diseases. In this article, we reviewed the current knowledge of the biology of IL-33 and discussed the roles of the IL-33 in regulating airway immune responses and allergic airway diseases.

IL‐33 signalling contributes to pollutant‐induced allergic airway inflammation

“…(A) C57BL/6J mice were intranasally exposed to saline (white bars), 25 μg DEP (striped bars), 1 μg HDM (checked bars) or combined DEP+HDM (black bars) on days 1, 8 and 15. Although under inflammatory conditions IL-33 can be induced in immune cells,8 we identified nonhematopoietic cells as the major IL-33 producers in our model of DEP-enhanced allergic airway inflammation, whereas ST2 was predominantly expressed on the hematopoietic cells. (B, C), IL-33 (B) and ST2 (C) mRNA expression in total lung tissue was determined using qRT-PCR.…”

“…3 The best characterized phenotype is allergic asthma, a type 2-mediated immune disorder caused by exposure to common inhaled allergens, such as house dust mite (HDM). [7][8][9] Several genome-wide association studies have shown that IL-33 and its receptor ST2 are associated with asthma susceptibility. It acts not only as a passive barrier but is also actively involved in respiratory defence through pro-inflammatory cytokine production.…”

IL-33/ST2 Axis Regulates Vasculogenic Mimicry via ERK1/2-MMP-2/9 Pathway in Melanoma

“…Chronic inflammation and tumors are closely related [25]. Inflammatory factors are an important feature of the tumor microenvironment.…”

“…Subsequent studies have confirmed that the presence of VM can compensate for endothelium-dependent blood vessels to provide nutrients to tumors to promote tumor progression [25, 26]. At the same time, it is also the reason why the angiogenesis inhibitor trials have been disappointing in treating tumors.…”

Protein Biomarkers in Asthma

“…IL-33 is important in the innate and adaptive immune response in the mucosal organs for chronic airway inflammation and tissue remodeling [54]. In innate immunity, IL-33 activates eosinophils, basophils, mast cells, and ILC2.…”