Stromal-Cell Derived Factor Is Expressed by Dendritic Cells and Endothelium in Human Skin

Abstract

Stromal-cell derived factor or SDF-1 is a CXC chemokine constitutively expressed by stromal bone marrow cell cultures that binds to the G-protein-coupled receptor CXCR4. SDF-1/CXCR4 represents a unique, nonpromiscuous ligand/receptor pair that plays an essential role in prenatal myelo- and lymphopoiesis as well as in cardiovascular and neural development. SDF-1 prevents entry of CXCR4-dependent (X4) HIV viruses in T lymphocytes, by binding and internalizing CXCR4. The expression pattern of SDF-1 protein in normal tissues is not known. Here we describe an analysis of SDF-1 mRNA and protein in normal and inflamed skin by in situ hybridization and immunohistochemistry, using a novel anti-SDF-1 monoclonal antibody. We also describe the expression pattern of CXCR4 receptor by immunohistochemistry. Our results show that SDF-1 protein and mRNA are normally expressed by endothelial cells, pericytes, and either resident or explanted CD1a+ dendritic cells. Epithelial cells of sweat glands but not keratinocytes also express SDF-1. In various inflammatory skin diseases, a large number of mononuclear cells and fibroblasts in close contact with CXCR4-positive lymphocytic infiltrates also express SDF-1. CXCR4 was also detected in many different normal cell types, including endothelial and epithelial cells, which points to a role for SDF-1/CXCR4 cell signaling in vascular and epithelial homeostasis. The demonstration of SDF-1 expression in dendritic and endothelial cells provides new insights into the mechanisms of normal and pathological lymphocyte circulation and makes it possible to envisage a role for locally secreted SDF-1 in the selective incapacity of mucosal dendritic cells to support and propagate infection by X4 HIV isolates.

Stromal Cell–Derived Factor-1 from Biliary Epithelial Cells Recruits CXCR4-Positive Cells: Implications for Inflammatory Liver Diseases

“…Roles for the SDF-1/CXCR4 interaction, other than normal homeostasis and development, have been reported recently in pathologic conditions such as rheumatoid arthritis (RA) , inflammatory skin diseases (Pablos et al, 1999), and skin wound healing (Fedyk et al, 2001). In the RA synovium, SDF-1 was expressed in cells with a fibroblastic appearance, whereas it was not expressed in the synovium of osteoarthritis.…”

“…Pablos et al (1999) reported that SDF-1 was expressed in fibroblasts close to or within dermal inflammatory infiltrates of inflammatory skin diseases, whereas it is confined to endothelial cells, pericytes, and dendritic cells, not fibroblasts, in normal human skin, suggesting that SDF-1 gene expression of skin fibroblasts is upregulated by proinflammatory stimuli. In contrast, Fedyk et al (2001) demonstrated that SDF-1 production by skin fibroblasts is inhibited by cytokines such as IL-1 and TNF-␣.…”

Haplotype analysis of the SDF-1 (CXCL12) gene in a longitudinal HIV-1/AIDS cohort study

“…1-3 SDF-1 is constitutively expressed by stromal, endothelial, dendritic, and other cells. [4][5][6] It stimulates the motility of hematopoietic cells, lymphocytes, and monocytes, 7,8 thymocytes, 9 and mediates leukocyte adhesion to the vascular endothelium. 10 SDF-1 also influences the development of microglia, astrocytes, and neurons.…”

The L1 major capsid protein of HPV16 differentially modulates APC trafficking according to the vaccination or natural infection context

“…By using a CXCR4 antagonist treatment, Kabashima et al demonstrated that the ligation of CXCR4 to its ligand CXCL12 plays also a key role for DC migration into draining lymph nodes in vivo. CXCL12 is expressed by stromal cells in the medulla of lymph nodes, in the red pulp of the spleen, in the bone marrow, and by skin endothelial cells [27,28]. Human DC themselves may also express CXCL12 [28], which has potent chemoattractant properties for lymphocytes expressing CXCR4 [29], suggesting that DC could also play a critical role in lymphocytic circulation.…”

“…CXCL12 is expressed by stromal cells in the medulla of lymph nodes, in the red pulp of the spleen, in the bone marrow, and by skin endothelial cells [27,28]. Human DC themselves may also express CXCL12 [28], which has potent chemoattractant properties for lymphocytes expressing CXCR4 [29], suggesting that DC could also play a critical role in lymphocytic circulation.Using a Boyden chamber assay, a significantly increased migratory capacity of DC activated by VLP or LPS was demonstrated in the presence of CXCL12. The recruitment of DC stimulated by VLP or LPS was also more important in the presence of HFM.…”