A Single-Cell Transcriptomic Profiling of the Effects of House Dust Mite Exposure on the Murine Lung Microenvironment
- Chang, Han
- Advisor(s): Raz, Eyal;
- Daugherty, Matthew
House Dust Mite (HDM) is a common aeroallergen that can induce asthma and allergic airway inflammation. The effects of acute exposure to HDM have been well studied in various mouse models asthma; however, the effects of chronic exposure have been much less investigated. Our studies identified that chronic exposure to HDM induces chronic lung inflammation and accelerates lung cancer development in two different mouse models of lung cancer. The lung cancer-promoting effect of HDM was mainly due to chronic activation of the NLRP3 inflammasome in lung macrophages and persistent production of IL-1β in the lungs. Based on these findings, we hypothesize that chronic exposure to HDM changes the lung microenvironment and makes it conducive to tumor growth by activating the IL-1β signaling pathway. To further evaluate the mechanisms by which HDM affects the lung microenvironment, we conducted a single-cell RNA sequencing (scRNA-seq) analysis and compared the effect of chronic HDM exposure in the lungs of wild-type (WT) and IL-1β knock out (KO) mice. Our findings suggest that HDM and IL-1β signaling affect various cell types such as macrophage, neutrophils, and T cells and their gene profiles that may contribute to the protumorigenic effects of HDM and IL-1β in the lungs. In conclusion, our study revealed the transcriptomic landscape of the murine lung microenvironment and uncovered the effects of chronic HDM exposure and IL-1β signaling.