title: Reduction of inflammatory slan (6-sulfo LacNAc) dendritic cells in psoriatic skin of patients treated with etanercept.
abstract: Dermal dendritic cells (DCs) play a central role in the immunopathology of psoriasis. We previously identified slanDCs as pro-inflammatory TNF-α, IL-23- and IL-12-producing DCs in human blood and as prominent inflammatory dermal TNF-α secreting and CD11c-positive DC subset in psoriasis. Here, we ask for the effects of TNF-α-inhibition on inflammatory slanDCs in skin and blood of 10 patients with psoriasis during 24 weeks of treatment with etanercept. Treatment with etanercept reduced the frequency of dermal slanDCs but did not induce apoptosis as determined by lack of increased active caspase-3-expression. In parallel, we found increased frequencies of slanDCs in blood which expressed lower levels of HLA-DR. Stimulating slanDCs isolated from the blood of healthy donors in vitro induced a strong production of IL-1β, IL-6, IL-23 and IL-12p70. This capacity was efficiently reduced in the presence of etanercept, thereby indicating that TNF-α is an autocrine stimulus for maturation and pro-inflammatory cytokine production of slanDCs. In vivo, we noticed that treatment with etanercept did reduce the number of dermal slanDCs in parallel to the overall expression of TNF-α and IL-23p19. However, successful treatment did not down-regulated the percentage of dermal slanDCs that stained positive for TNF-α and IL-23p19 indicating that remaining slanDCs kept their pro-inflammatory capacity. This study provides novel insights into the immune regulatory properties of etanercept at the level of inflammatory slanDCs in vivo in skin and blood as well as in vitro.
authors.affiliation: Department of Dermatology, Technical University of Dresden, University Hospital, Dresden, Germany. claudia.guenther@uniklinikum-dresden.de
authors.forename: Claudia
authors.initials: C
authors.lastname: Günther
authors.forename: Kristin
authors.initials: K
authors.lastname: Blau
authors.forename: Ulrike
authors.initials: U
authors.lastname: Förster
authors.forename: Antje
authors.initials: A
authors.lastname: Viehweg
authors.forename: Gottfried
authors.initials: G
authors.lastname: Wozel
authors.forename: Knut
authors.initials: K
authors.lastname: Schäkel
mesh_terms: D000328:Adult; D000368:Aged; D000606:Amino Sugars / Q000097:blood*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects*; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy*; D053759:Interleukin-23 / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy*; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C467438:6-sulfo-LacNac; D000606:Amino Sugars; D007074:Immunoglobulin G; D007155:Immunologic Factors; D053759:Interleukin-23; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; C505407:CASP3 protein, human; D053148:Caspase 3; D000068800:Etanercept
keywords: TNF-alpha; etanercept; psoriasis; skin; slan dendritic cells