A stromal address code defined by fibroblasts

Rheumatology Research Group, Institute of Biomedical Research, MRC Center for Immune Regulation, University of Birmingham, UK, B15 2TT.
Trends in Immunology (Impact Factor: 10.4). 04/2005; 26(3):150-6. DOI: 10.1016/
Source: PubMed


To navigate into and within tissues, leukocytes require guidance cues that enable them to recognize which tissues to enter and which to avoid. Such cues are partly provided at the time of extravasation from blood by an endothelial address code on the luminal surface of the vascular endothelium. Here, we review the evidence that fibroblasts help define an additional stromal address code that directs leukocyte behaviour within tissues. We examine how this stromal code regulates site-specific leukocyte accumulation, differentiation and survival in a variety of physiological stromal niches, and how the aberrant expression of components of this code in the wrong tissue at the wrong time contributes to the persistence of chronic inflammatory diseases.

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Available from: Christopher D Buckley, May 17, 2014
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    • "Common mechanisms occur in these fibrotic processes that include persistent inflammation and local overproduction/activation of different cytokines (Ghosh and Vaughan, 2012; Huang and Ogawa, 2012). For example, infiltrating immune cells in DD excrete large amount of different cytokines, chemokines and growth factors, especially TGF-β1 (Baird et al., 1993), cytokine that induces typical phenotypic changes and inflammation (Parsonage et al., 2005; Lupher and Gallatin, 2006). Under such conditions, cells may acquire myofibroblast phenotype. "
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    ABSTRACT: Objectives: Inflammation is an underlying mechanism behind fibrotic processes and differentiation of cells into myofibroblasts. Presented study therefore provides new data on activation of autoimmune and inflammatory immune response genes that accompany activation of p38 and cell differentiation in primary cells derived from Dupuytren's disease (DD) patients. Methods: Primary non-Dupuytren's disease cells (ND) were isolated from macroscopically unaffected palmar fascia adjacent to diseased tissue obtained from patients diagnosed with the last stage of DD and cultured in vitro. Gene expression, collagen gel contraction assay and analysis of secreted proteins were performed in ND cells treated with TGF-β1 and/or inhibitor of p38 phosphorylation. Results: During differentiation of ND fibroblasts, increased expression of immune response genes PAI-1, TIMP-1, CCL11, and IL-6 was found. These changes were accompanied by increased cell contractility and activation of p38 and its target kinase MK2. Inhibition of p38 phosphorylation reversed these processes in vitro. Conclusions: TGF-β1 induced p38 phosphorylation in ND cells grown from macroscopically unaffected palmar fascia adjacent to diseased tissue from DD patients. This was accompanied by activation of the cytokine genes CCL-11 and IL-6 and secretion of extracellular matrix regulatory proteins PAI-1 and TIMP-1. A combined approach directed toward inflammation and p38 MAPK-mediated processes in DD might be considered for improving management of DD patients and prevention of recurrence.
    Full-text · Article · Dec 2015
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    • "Interestingly, homeobox (HOX) gene expression was differentially expressed according to the location where the fibroblasts were isolated. These data suggest that the geneexpression profile of adult fibroblasts may play a significant role in assigning positional identity within an organism and has lent support to the proposal of a stromal address code that can direct leukocyte behaviour (Parsonage et al., 2005). "

    Full-text · Dataset · Jul 2015
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    • "However, in recent years it has become clear that fibroblasts embedded in peritoneal interstitium act not only as structural cells but may also serve as an important source of chemokines [7]. Thus, by producing various chemokines fibroblasts may modify both the intensity and the duration of the inflammatory response [8]. We have previously demonstrated that human peritoneal fibroblasts (HPFB) generate significant quantities of CXC chemokines that attract and promote survival of PMN during PD-associated peritonitis [9]. "
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    ABSTRACT: Peritonitis is characterized by a coordinated influx of various leukocyte subpopulations. The pattern of leukocyte recruitment is controlled by chemokines secreted primarily by peritoneal mesothelial cells and macrophages. We have previously demonstrated that some chemokines may be also produced by human peritoneal fibroblasts (HPFB). Aim of our study was to assess the potential of HPFB in culture to release CCL5, a potent chemoattractant for mononuclear leukocytes. Quiescent HPFB released constitutively no or trace amounts of CCL5. Stimulation of HPFB with IL-1 β and TNF- α resulted in a time- (up to 96 h) and dose-dependent increase in CCL5 expression and release. IFN- γ alone did not induce CCL5 secretion over a wide range of concentrations (0.01-100 U/mL). However, it synergistically amplified the effects of TNF- α and IL-1 β through upregulation of CCL5 mRNA. Moreover, pretreatment of cells with IFN- γ upregulated CD40 receptor, which enabled HPFB to respond to a recombinant ligand of CD40 (CD40L). Exposure of IFN- γ -treated HPFB, but not of control cells, to CD40L resulted in a dose-dependent induction of CCL5. These data demonstrate that HPFB synthesise CCL5 in response to inflammatory mediators present in the inflamed peritoneal cavity. HPFB-derived CCL5 may thus contribute to the intraperitoneal recruitment of mononuclear leukocytes during peritonitis.
    Full-text · Article · Jan 2014 · Mediators of Inflammation
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