The inhibition of IL-33 and its role in mast cell dependent allergic asthma

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Scientific Abstract Background: Asthma is a chronic disease identified by the consistent occurrence of bronchospasms in the airway in addition to airway inflammation and mucus hypersecretion. Allergy-induced asthma is the most common type of asthma, which is predominantly caused by the T-helper 2 cell response. Mast cells are innate immune cells that play an essential role in the allergic reactions and facilitate host defense against allergen agents. They are primarily located in vascular tissues. Interlukin-33 is a new cytokine that belongs to the IL-1 family and is considered an alarmin cytokine that is released from epithelial cells in response to pathogens. IL-33 binds to its receptor ST2 and is expressed by various immune cells, such as mast cells. Methodology: An extensive search was conducted on Web of Science, ProQuest, Ovid, and EBSCO platforms to evaluate all the studies that have assessed the role of IL-33/ST2 axis in both Th2 and mast cells responses in the context of allergic asthma. Ultimately, 12 studies involving only human and mice models were selected for this research. Results: Stage one, which evaluated the studies that investigated the Th2 cell in response to IL-33/ST2 pathway, demonstrated that either endogenous or exogenous IL-33s induced a Th2 response through the production of IL-5 and IL-13 cytokines. Whereas, stage two, which examined the studies that have assessed the influence of IL-33/ST2 on mast cells, revealed a potential role of mast cells in allergic asthma. The mast cells responded to IL-33 by either releasing mediators or pro-inflammatory cytokines. Most studies revealed that blocking experiments successfully inhibited the immune response of the IL-33/ST2 axis. Conclusion: Due to the divergent effects of IL-33 on mast cells in allergic asthma, inhibiting the IL-33/ST2 signaling pathway might significantly represent an effective treatment for allergic asthma. This will improve the life quality of asthmatic patients. Lay abstract Background: Asthma is characterized by air passage inflammation, excessive mucus secretion, and the remodeling of lung compartments, which causes breathing difficulties. There are various types of asthma, but allergic asthma is the most common. A central immune cell, called “T-helper 2,” is the main cause of the allergic response. Under allergic conditions, a type of immune cells, called “mast cells,” response rapidly to allergens. These cells are found in the tissues that face the external environment. Interleukin (IL) 33 is an alarmin protein that is secreted from damaged cells when foreign substances penetrate barrier tissues. This protein needs to bind to a specific part, called ST2, found in immune cells such as mast cells. Methodology: Four platforms named Web of Science, ProQuest, Ovid, and EBSCO were searched to evaluate all the studies that have examined the function of IL-33 that affected both the Th2 and mast cells in allergic asthma. A total of 12 studies were selected, which included only human and mice studies. Results: The results of the studies were divided into two stages: The first and second stages evaluated the studies that assessed the response of Th2 and the mast cell response to IL-33, respectively. The findings of these stages revealed that, both inside and outside, IL-33 activated the immune response of Th2 and mast cells. The Th2 cells produced proteins called IL-5 and IL-13, which are highly linked to allergic asthma, while the mast cells secreted substances that cause the allergic reaction. The blocking of IL-33 or its binding part (ST2) stopped the immune response. Conclusion: As IL-33 plays several roles that affect mast cells functions in allergic asthma, it is promised to inhibit the IL-33 function to help asthma patients. A new treatment could be generated based on these findings.

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