Abstract
The bleomycin mouse model is the most extensively used animal model to study pulmonary fibrosis. Despite this, the inflammatory cell kinetics and cell compartmentalisation is still incompletely understood. Here we simultaneously analysed 16 inflammatory cell populations in 303 samples and applied advanced data modelling to conclusively detail these kinetics.
Three days post-bleomycin, the inflammatory profile was typified by acute innate inflammation, pronounced neutrophilia and loss of alveolar macrophages. After 14 days, rapid responders were increasingly replaced by the adaptive immune system and monocyte-derived alveolar macrophages, which progressed till 21 days. Multi-colour imaging revealed the spatial-temporal cell distribution and the close association of T-cells with fibrotic lung tissue at later time-points.
Unbiased immunophenotyping and data modelling exposed the dynamic shifts in immune cell composition distinct for each phase of fibrosis process and defined the transition from innate to adaptive immunity marking initial lung parenchyma remodelling.
One Sentence Summary Unbiased immunophenotyping and data modelling exposed the dynamic shifts in immune cell composition during bleomycin induced pulmonary fibrosis.
Competing Interest Statement
The authors have declared no competing interest.
Abbreviations
- BALF
- bronchoalveolar lavage fluid
- BH
- Benjamini-Hochberg
- FCM
- flow cytometry
- IPF
- idiopathic pulmonary fibrosis
- LOGx+1
- logarithm to the basis 10 of (x+1)
- ML
- maximum likelihood
- MVA
- multivariate analysis
- NLME
- non-linear mixed models
- OPLS-DA
- orthogonal projections to latent structures discriminant analysis
- PCA
- principal component analysis
- PF
- pulmonary fibrosis
- UMAP
- Uniform Manifold Approximation and Projection
- UVA
- univariate analysis
- 4RT
- fourth root