Spatial Colocalization and Remodeling of Communication Patterns between CD4 Th2 Cells and Fibroblasts in the Asthmatic Bronchial Microenvironment

Background: Type 2 inflammation is a hallmark of allergic asthma, and the central role of CD4 Th2 cells in this process is well established. Nevertheless, how CD4 Th2 cells spatially organize and interact with structural cells within tissues to promote airway microenvironment remodeling remains unclear. Methods: In this research, we employed 10x Genomics Visium spatial transcriptomics technology to examine spatial gene expression patterns in lung tissues from a mouse model of asthma induced by house dust mite (HDM). By integrating the SPOTlight algorithm with single-cell transcriptomic reference data, we conducted cell type deconvolution of spatial spots, developed spatial feature scores for CD4 Th2 cells and fibroblasts, and utilized spatially constrained CellChat analysis to deduce ligand-receptor communication between these two cell types in the bronchial microenvironment. Results: Our findings revealed that in asthmatic conditions, CD4 Th2 cells transitioned from a scattered distribution to notable clustering around the bronchi, exhibiting specific spatial co-localization with fibroblasts in the bronchial area (correlation coefficient R=0.19, P=0.0023). In contrast, no positive correlation was found between these cells in non-bronchial regions (R=-0.1, P=0.0001). Further cell communication analysis showed that under normal conditions, interactions between CD4 Th2 cells and fibroblasts were mainly driven by extracellular matrix (ECM)-related signals, particularly the Collagen-Integrin pathway. However, in asthma, this interaction pattern shifted to a pathological form characterized by Cdh1-Cdh1 mediated cell adhesion signaling. Conclusion: This study illustrates that CD4 Th2 cells and fibroblasts establish region-specific spatial cooperative relationships within the asthmatic bronchial microenvironment, with their communication patterns evolving from maintaining tissue structure to facilitating immune cell anchoring and adhesion. These insights offer a novel perspective on the spatial coupling mechanisms underlying type 2 inflammation and airway remodeling.