Figure 1

Dynamic/temporal local micro-environmental niche. The CXCR4-expressing fibrocytes are recruited from the circulation to the tissue by a gradient of stromal cell-derived factor (SDF)-1/CXCL12. In the tissue the fibrocytes move and interact with the dynamic/temporal local micro-environmental niche consisting of a broad array of extracellular matrix (ECM) molecules such as collagens, proteoglycans, hyaluronan, and glycoproteins. The ECM forms a network and acts as a supporting structure for tissue integrity. It is very essential that the ECM can also function as a reservoir for a large number of growth factors and cytokines, e.g., SDF-1/CXCL12, transforming growth factor (TGF)-β, interleukin (IL)-8, tumor necrosis factor (TNF)-α, platelet-derived growth factor (PDGF), and vascular endothelial growth factor (VEGF), just to mention some examples (generalized as violet spots in the figure) [55, 56]. However, in disease states, the structure and composition of the ECM is changed, and that strongly affects the activity of cells in the niche. The alteration of the ECM, of course, is dependent on type of disease, state of disease, gene signature, age, gender, nutrition, infection, and also physical location in the pulmonary tree. It is important that the expression of the haematopoietic surface receptors, CD34, CD45, and CXCR4, on the fibrocytes gradually decreases, whereas the expression of the mesenchymal markers, such as collagen, fibronectin, and proteoglycans, gradually increases during the fibrocytes' journey through the tissue. The fibrocyte can also migrate to the lumen of the airway, and it has been detected there in both asthma and IPF.