title: Attenuated TGF-β1 responsiveness of dendritic cells and their precursors in atopic dermatitis.
abstract: The responsiveness of DCs and their precursors to transforming growth factor beta1 (TGF-β1) affects the nature of differentiating DC subsets, which are essential for the severity of atopic dermatitis (AD). To evaluate TGF-β signaling in monocytes and monocyte-derived DCs of AD patients compared with that of controls, in vitro generated Langerhans cell (LC) like DCs, expression of TGF-β receptors, phospho-Smad2/3 and Smad7 were evaluated. Furthermore, TNF-α expression and synergistic effects of TNF-α upon TGF-β signaling and DC generation were evaluated. We found LC-like DC differentiation of monocytes from AD patients in response to TGF-β1 was remarkably reduced and TGF-β1 receptor expression was significantly lower compared with that of healthy controls. Attenuated TGF-β1 responsiveness mirrored by lower phospho-Smad2/3 expression after TGF-β1 stimulation and higher expression of inhibitory Smad7 was observed in monocytes from AD patients. During DC generation, mRNA expression of Smad7 was relatively higher in LC-like DCs of AD patients. Lower TNF-α expression of monocytes from AD patients might further contribute to attenuated TGF-β signaling in the disease since TNF-α had synergistic effects on TGF-β1 signaling and LC generation through mediating the degradation of Smad7. Our results demonstrate alleviated TGF-β1 signaling together with the amount of soluble co-factors might direct the nature of differentiating DCs.
authors: Department of Dermatology and Allergy, University of Bonn, Bonn, Germany.
authors: Wen-Ming
authors: WM
authors: Peng
authors: Laura
authors: L
authors: Maintz
authors: Jean-Pierre
authors: JP
authors: Allam
authors: Natalija
authors: N
authors: Novak
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007801:Langerhans Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000235:genetics / Q000276:immunology; D051900:Smad3 Protein / Q000235:genetics / Q000276:immunology; D051906:Smad7 Protein / Q000235:genetics / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: D018125:Receptors, Transforming Growth Factor beta; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; C497806:SMAD7 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D051906:Smad7 Protein; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha