Psoriasis scales contain C5a as the predominant chemotaxin for monocyte-derived dendritic cells

Dendritic cells seem to be of major importance for the pathogenesis of psoriasis. They are increased in number in lesional psoriatic skin which is thought to be due to an increased influx from the peripheral blood regulated by chemotaxins. Using a biological/biochemical approach we have addressed the question whether psoriasis scale extracts contain proteinaceous chemotaxins for dendritic cells. Human monocytes differentiated into dendritic cells by culture with GM-CSF and IL-4 (MoDC) served as responder cells. Chemotactic activity for MoDC was purified by several HPLC-steps. The results of our study show that C5a/C5adesarg is the major chemotactic peptide for MoDC in psoriasis scale extracts. In comparison to other stimuli such as fMLP or monocyte chemotactic peptide 1 (MCP-1) C5a proved to be a most potent and efficient chemotaxin for MoDC. C5a co-eluted with MRP14/calgranulin B which is present in large amounts in psoriasis scale extracts as identified by amino acid sequencing. However, MRP14/calgranulin B did not possess any chemotactic activity for MoDC. Our results provide evidence that C5a/C5adesarg although not specific for dendritic cells seems to be the major chemoattractant for these cells in lesional psoriasis skin.     

Infliximab reduces activated myeloid dendritic cells,different macrophage subsets and CXCR3‐positive cells in granuloma annulare

Disseminated granuloma annulare (GA) is a rare granulomatous dermatitis of unknown etiology. Treatment is often challenging and lack of a uniformly effective treatment, adds to the disease morbidity. Tumor necrosis factor (TNF)‐α is an important cytokine in granuloma formation and previous reports have shown improvement of disseminated GA with anti‐TNF‐α therapy. Nevertheless, the underlying mechanism of actions of TNF‐α inhibitors in GA remains unclear. Our aim was to evaluate alterations in the inflammatory infiltrate in a patient who experienced complete clearance of GA after treatment with infliximab. A skin biopsy was obtained before and 24 weeks after treatment with infliximab 5 mg/kg at weeks 0, 2, 6, 14 and 24. Immunohistochemical stains were performed in pre‐ and post‐treatment biopsy specimens using CD1a, CD4, CD8, CD11c, CD32, CD68, CD69, CD163, CD183 and human leukocyte antigen (HLA)‐DR to characterize alterations of the infiltrates. Parallel with clinical improvement, we observed a marked decrease in myeloid (CD11c) dendritic cells, different macrophage subsets (CD68, CD32, CD163) and T cells. In addition, a marked reduction of activation markers (HLA‐DR, CD69) and CD183⁺ (CXCR3) cells was observed in post‐treatment biopsy specimens. In conclusion, the clinical improvement of disseminated GA by infliximab is paralleled by inhibition of activated myeloid dendritic cells, different macrophage subsets and type 1 T cells.