Single-cell transcriptomic analysis reveals the immune landscape of lung in steroid-resistant asthma exacerbation

Abstract

Exaggerated airway hyperresponsiveness and inflammation are hallmarks of asthma, and lipopolysaccharide (LPS) exposure is linked to the severity of the disease and steroid resistance. To investigate the mechanisms underlying asthma exacerbation, we established a mouse model of LPS-induced steroid-resistant exacerbation on the background of house dust mite (HDM)-induced asthma to profile the immune cells in lung by using single-cell RNA deep sequencing. Twenty immune subsets were identified by their molecular and functional properties. Specific cell clusters of basophils, type 2 innate lymphoid cells (ILC2), and CD8+ memory T cells were the predominant sources of interleukin (IL)-4 and IL-13 transcripts whose expressions were dexamethasone resistant. Production of IL-13 by these cells was validated by IL-13-reporter mice. Neutralization of IL-13 abolished HDM/LPS-induced airway hyperresponsiveness, airway inflammation, and decreased mucus hypersecretion. Furthermore, using Ingenuity Pathway Analysis systems, we identified canonical pathways and upstream regulators that regulate the activation of basophils, ILC2, and CD8+ memory T cells. Our study provides mechanistic insights and an important reference resource for further understanding of the immune landscape during asthma exacerbation.

Single-Oocyte Gene Expression Suggests That Curcumin Can Protect the Ovarian Reserve by Regulating the PTEN-AKT-FOXO3a Pathway

“…In order to identify new drugs that can regulate the activation of follicles, we used IPA for bioinformatics analysis of gene expression profiles. IPA is a commonly used tool for signal pathway research and drug screening [ 34 ], and core analysis in IPA is often used to predict upstream regulatory factors and drugs in various research fields [ 35 , 36 , 37 ]. For example, by using IPA to analyze the differences in the transcriptomes of follicular development in vitro and in vivo, a previous study predicted follicular development-related signaling pathways and drugs and found that adding an estrogen-receptor antagonist to cultured ovarian tissue (ICI 182,780) can overcome hypoplastic follicular development in vitro [ 37 ].…”

Systematic Characterization of the Group 2 House Dust Mite Allergen in Dermatophagoides microceras

“…And the quantity of endogenous LPS in M2Q used for this animal study was less than 0.1 μg (<50 ng). In another study, Wang et al. (2021) used 50 μg crude Der p with 50 ng LPS to sensitize mice, and the results showed that LPS did not affect the level of HDM-induced infiltrated eosinophil and lymphocyte in mouse BALF.…”

Integrative Analysis of Spatial Transcriptome with Single-cell Transcriptome and Single-cell Epigenome in Mouse Lungs after Immunization

“…As the development of single-cell sequencing technologies, scRNA-seq has been gradually applied to study immune cells and immune responses in mouse lungs (Ballesteros et al, 2020;Cohen et al, 2018;Kurihara et al, 2021;Wang et al, 2021). In many cases, T helper cells and cytotoxic T cells can be identified in these scRNA-seq studies, but not their subtypes.…”