Extracellular matrix phenotyping by imaging mass cytometry defines distinct cellular matrix environments associated with allergic airway inflammation.

Abstract

The extracellular matrix (ECM) forms the scaffold in which cells reside and interact. The composition of this scaffold guides the development of local immune responses and tissue function. With the advent of multiplexed spatial imaging methodologies, investigating the intricacies of cellular spatial organisation are more accessible than ever. However, the relationship between cellular organisation and ECM composition has been broadly overlooked. Using imaging mass cytometry, we investigated the association between cellular niches and their surrounding matrix environment during allergic airway inflammation in two commonly used mouse strains. By first classifying cells according to their canonical intracellular markers and then by developing a novel analysis pipeline to independently characterise a cells ECM environment, we integrated analysis of both intracellular and extracellular data. Applying this methodology to three distinct tissue regions we reveal disparate and restricted responses. Recruited neutrophils were dispersed within the alveolar parenchyma, alongside a loss of alveolar type I cells and an expansion of alveolar type II cells. This activated parenchyma was associated with increased proximity to hyaluronan and chondroitin sulphate. In contrast, infiltrating CD11b+ and MHCII+ cells accumulated in the adventitial cuff and aligned with an expansion of the subepithelial layer. This expanded subepithelial region was enriched for closely interacting stromal and CD11b+ immune cells which overlaid regions enriched for type-I and type-III collagen. The cell-cell and cell-matrix interactions identified here will provide a greater understanding of the mechanisms and regulation of allergic disease progression across different inbred mouse strains and provide specific pathways to target aspects of remodelling during allergic pathology. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=135 SRC="FIGDIR/small/623782v2_ufig1.gif" ALT="Figure 1"> View larger version (58K): org.highwire.dtl.DTLVardef@dcaf56org.highwire.dtl.DTLVardef@7b5d7forg.highwire.dtl.DTLVardef@1376d4eorg.highwire.dtl.DTLVardef@1e95801_HPS_FORMAT_FIGEXP M_FIG C_FIG