Fig. 5: FABP4⁺ and SPP1⁺ macrophages accumulate in PF airspaces and are characterized by a spatial niche.

a, Boxplot showing the proportion of cells assigned to the C11 niche across disease severity, including unaffected (n = 10), less affected (n = 15) and more affected (n = 20) samples. b, Representative example of cell niches, including the C11 macrophage accumulation niche (light blue) in sample VUILD102LA (IPF). c, FABP4⁺ and SPP1⁺ macrophages in minimally remodeled alveoli, including FABP4⁺ macrophages accumulated within an alveolus (denoted by a square bracket). Instances of individual FABP4⁺ macrophages that have migrated into alveolar lumens and small FABP4⁺ accumulations (black arrows) and SPP1⁺ macrophages in the interstitium (white arrows) are marked noncomprehensively. d,e, H&E images of FABP4⁺ (d) and SPP1⁺ (e) macrophage accumulations within airways and substantially remodeled distal airspaces overlain with transcript expression for listed genes. f, Distribution of macrophage subtypes as a proportion of the total population of macrophages across disease severity. g,h, Matched Xenium and Visium HD images of FABP4⁺ (g) and mixed FABP4⁺/SPP1⁺ (h) macrophage accumulations within distal airspaces. For g, the Visium HD image (right) shows the sum of the log₂ expression of a list of genes marking alveolar macrophages as a density map overlain on the H&E. In h, the sum log₂ expression of a list of genes marking alveolar macrophages is compared to a list marking SPP1⁺ macrophages. Genes that were strong markers for both alveolar and SPP1⁺ macrophages were not included in h. See Methods for the gene selection process and Supplementary Table 10 for a list of marker genes. For c–e,g,h Xenium images, all listed genes are potentially visible in each example image if expressed, except SCGB3A2, which for clarity is not shown on the two figures that include airways, and AGER, which is only shown in d. Scale bars on the bottom left of each H&E = 20 µm. c, Sample TILD130LA (IPF); d, examples from VUILD91MA (top; IPF) and VUILD96LA (bottom; sarcoidosis); e, samples VUILD78MA (top; IPAF) and VUILD96MA (bottom; sarcoidosis) and g,h, sample VUILD49LA (cHP).