Single-cell transcriptomics reveals immune remodeling of the murine lung microenvironment following chronic house dust mite exposure.

Introduction: House dust mite (HDM) is a common environmental aeroallergen strongly associated with asthma and chronic airway inflammation. While HDM exposure is known to induce T helper 2 (Th2)-mediated eosinophilic inflammation, its chronic effects on interleukin-1β (IL-1β)-associated neutrophilic inflammation remain poorly understood. This study used single-cell RNA sequencing (scRNA-seq) to investigate how chronic HDM exposure remodels the murine lung immune microenvironment, with a focus on the role of IL-1β in shaping HDM-driven immune responses. Methods: Wild-type and Results: Our analysis demonstrates that chronic HDM exposure promotes the recruitment and activation of diverse immune cell populations in the lungs, including neutrophils, M2-polarized macrophages, B-2 (follicular) B cells, and multiple subsets of regulatory and effector CD4⁺ T cells. These populations contribute differently to the development or resolution of chronic lung inflammation through IL-1β-dependent and -independent mechanisms. scRNA-seq indicated that IL-1β signaling is critical for sustaining neutrophil and Th17 responses, whereas Discussion: These findings demonstrate that chronic HDM exposure profoundly remodels the lung immune microenvironment through IL-1β-dependent and -independent mechanisms. The effects are context-dependent and modulated by the endotoxin content of HDM extracts, highlighting the complex immunomodulatory effects of HDM in inducing chronic lung inflammation.