Fibrocytes Are Not an Essential Source of Type I Collagen during Lung Fibrosis

Abstract

Progressive fibrosis involves accumulation of activated collagen producing mesenchymal cells. Fibrocytes are hematopoietic-derived cells with mesenchymal features that potentially have a unique and critical function during fibrosis. Fibrocytes have been proposed as an important direct contributor of type I collagen deposition during fibrosis based largely on fate-mapping studies. To determine the functional contribution of hematopoietic cell-derived type I collagen to fibrogenesis we utilize a double transgenic system to specifically delete the type I collagen gene across a broad population of hematopoietic cells. These mice develop a robust fibrotic response similar to littermate genotype control mice injured with bleomycin indicating that fibrocytes are not a necessary source of type I collagen. Using collagen-promoter GFP mice we find that fibrocytes express type I collagen. However, fibrocytes with confirmed deletion of the type I collagen gene have readily detectable intracellular type I collagen indicating that uptake of collagen from neighboring cells account for much of the fibrocyte collagen. Collectively these results clarify several seemingly conflicting reports regarding the direct contribution of fibrocytes to collagen deposition.

PD-1 up-regulation on CD4 + T cells promotes pulmonary fibrosis through STAT3-mediated IL-17A and TGF-β1 production

“…Figure S7A depicts the gating strategy using flow cytometry. During analysis, we gated out CD3 + CD4 + T cells and used the absence of CD45 expression to identify the fibroblast population as established previously (21, 22). …”

TSLP Is a Potential Initiator of Collagen Synthesis and an Activator of CXCR4/SDF-1 Axis in Keloid Pathogenesis

“…Increased numbers of fibrocytes correlate with worsened disease progression in a bleomycin-induced lung fibrosis mouse model (Phillips et al, 2004). Furthermore, fibrocytes might function in fibrogenesis via paracrine actions that affect other collagen-producing cells (Kleaveland et al, 2014). In the skin, fibrocytes are detected in skin wounds, hypertrophic scars, keloids, and the skin of patients with nephrogenic systemic fibrosis (Iqbal et al, 2012;Sakai et al, 2006;Yang et al, 2002Yang et al, , 2005.…”

Two-Way Conversion between Lipogenic and Myogenic Fibroblastic Phenotypes Marks the Progression and Resolution of Lung Fibrosis

“…Other studies investigated the possibility that they originate from bone-marrow-derived CD45 + COL1 + CXCR4 + circulating fibrocytes (Phillips et al, 2004) that are recruited to the lungs. However, this scenario remains controversial (Kleaveland et al, 2014). Many studies hypothesized that myofibroblasts derive from epithelial cells undergoing epithelial-to-mesenchymal transition (EMT).…”