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

ABSTRACT 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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    • "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). "
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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.
    Mediators of Inflammation 01/2014; 2014:590654. DOI:10.1155/2014/590654 · 3.24 Impact Factor
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    • "Fibroblasts isolated from different tissues display similar morphology but exhibit diverse functional properties. For example, the capacity of fibroblasts from different anatomical sites to migrate or express extracellular matrix proteins varies [17]. These differences are consistent with the wide variety of biological and physical environments these cells are found in. "
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    ABSTRACT: Scleroderma (systemic sclerosis; SSc) is characterised by fibrosis of the skin and internal organs in the context of autoimmunity and vascular perturbation. Overproduction of extracellular matrix components and loss of specialised epithelial structures are analogous to the process of scar formation after tissue injury. Fibroblasts are the resident cells of connective tissue that become activated at sites of damage and are likely to be important effector cells in SSc. Differentiation into myofibroblasts is a hallmark process, although the mechanisms and cellular origins of this important fibroblastic cell are still unclear. This article reviews fibroblast biology in the context of SSc and highlights the potentially important place of fibroblast effector cells in fibrosis. Moreover, the heterogeneity of fibroblast properties, multiplicity of regulatory pathways and diversity of origin for myofibroblasts may underpin clinical diversity in SSc, and provide novel avenues for targeted therapy.
    Arthritis research & therapy 06/2013; 15(3):215. DOI:10.1186/ar4230 · 3.75 Impact Factor
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