Cross‐talk of four types of RNA modification writers defines the immune microenvironment in severe asthma

Abstract

Adenine modifications, including m 6 A, m 1 A, APA, and A-to-I modifications, are the most impactful RNA modifications. These modifications are primarily produced by enzymes called writers. The main purpose of this study was to explore the cross-talk and potential roles of these writers in severe asthma. We found 13 RNA writers potentially related to severe asthma and three RNA modification patterns. Cluster 3 showed predominant neutrophil infiltration and C-type lectin receptor signaling; cluster 1 showed predominant innate immune cell infiltration and ubiquitin-proteasome system activation; and cluster 2 did not show obvious immune infiltration characteristics.We found that RNA modification writers modified immune cell-related genes and led to both accumulation of different immune cells in the airways and activation of a series of biological processes, which ultimately leads to severe asthma. TRMT6, WTAP, and TRMT6A were included in a random forest model as predictors. Cromoglicic acid, thioperamide, and fluvastatin were potential drugs for clusters 1, 2, and 3, respectively. We found that cross-talk of RNA modifications is significant in severe asthma, which provides insight into severe asthma pathogenesis and possible treatment avenues.

Exploration and Validation of Potential Biomarkers and Therapeutic Targets in Ferroptosis of Asthma

“…Studies had shown a strong connection between asthma and the immune microenvironment. 25 , 26 Consequently, we next used the GSE41861 database in the Cibersort package to predict the proportion of 22 immune infiltrating cells in the immune microenvironment of asthma. The results are shown in Figure 8A , the percentages of dendritic cells activated, plasma cells, T cells CD4 memory activated and mast cells activated in asthma were higher than controls, while macrophages M2, T cells regulatory (Tregs) and T cells follicular helper were lower.…”