Deciphering the role of Interleukin-33, a Janus-Faced cytokine, in mast cell-mediated responses in allergic asthma using systems immunological methodologies

Abstract

Abstract The prevalence of Allergy and Asthma has been increasing over the past decade, and about 300 million people suffer from these diseases worldwide. Interleukin-33 (IL-33), an Interleukin-1 family of cytokine, binds with the IL-33 receptor (IL-33R) to elicit an array of molecular and cellular processes in immune cells. Here, we have studied the role of IL-33 in mast cell-mediated responses and its impact on allergic asthma using systems immunological methodologies. We have obtained all the microarray datasets from the Gene Expression Omnibus (GEO) related to the IL-33 treated mast cells and allergic asthma. The datasets were analyzed using Genespring GX12.6 (Agilent Technologies, USA) to classify the differentially expressed genes (P<0.05) compared to untreated controls. The ingenuity pathway analysis (Qiagen, USA) of the IL-33 triggered differentially expressed genes in mast cells have revealed that the canonical pathways such as T-helper cell differentiation, the role of macrophages, fibroblasts, endothelial cells in autoimmunity, and chemokine signaling were significantly (P<0.05) upregulated. Besides, in-depth analyses of the IL-33 induced differentially expressed genes in mast cells and allergic asthma, using the comparison analysis module in IPA, showed a significant attenuation in HCK and other related signaling networks. However, the stimulation of both Th1 and Th2 associated cytokines by IL-33 could differentially regulate allergic asthma. Thus, IL-33 is a Janus-Faced cytokine in mast cell mediated allergic responses and, hence, requires further in vitro and in vivo studies to evaluate the therapeutic importance.