Interleukin-33 mediated regulation of microRNAs in human cord blood-derived mast cells: Implications for infection, immunity, and inflammation

by Sherin Bakhashab, Ghalya H. Banafea, Farid Ahmed, Nadia Bagatian, Ohoud Subhi, Hans-Juergen Schulten, Peter Natesan Pushparaj

Mast cell (MCs) activation is the driving force of immune responses in several inflammatory diseases, including asthma and allergies. MCs are immune cells found throughout the body and are equipped with numerous surface receptors that allow them to respond to external signals from parasites and bacteria as well as to intrinsic signals such as cytokines. Upon activation, MCs release various mediators and proteases that contribute to inflammation. This study aimed to identify microRNAs (miRNAs) that regulate MC response to interleukin-33 and their target genes using a model of human cord blood-derived mast cells (hCBMCs). hCBMCs were induced with 10 and 20 ng of recombinant human interleukin-33 (rhIL-33) for 6 and 24 h, respectively. Total RNA was extracted from these cells and miRNA profiling was performed using high-throughput microarrays. Differential expression of miRNAs and target analysis were performed using Transcriptome Analysis Console and Ingenuity Pathway Analysis. The most significant miRNAs in each condition were miR-6836-5p (fold change = 1.76, p = 3E-03), miR-6883-5p (fold change = -2.13, p = 7E-05), miR-1229-5p (fold change = 2.46, p = 8E-04), and miR-3613-5p (fold change = 66.7, p = 1E-06). Target analysis revealed that these miRNAs regulate mast cell responsiveness and degranulation by modulating the expression of surface receptors, adaptors, and signaling molecules in response to rhIL-33 stimulation. This study is the first miRNA profiling and target analysis of hCBMCs that will further enhance our understanding of the role of miRNAs in the immune response in a timely manner and their relevance for the development of a new therapeutic target for inflammatory disorders.