Attenuated TGF-β1 responsiveness of dendritic cells and their precursors in atopic dermatitis

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.