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Recent evidence suggests that crosstalk between mast cells, nerves and keratinocytes might be involved in the exacerbation of inflammatory conditions by stress, but the mechanism by which this occurs remains unclear. Corticotropin-releasing factor (CRF), which activates the hypothalamo-pituitary-adrenal (HPA) axis under stress, also has pro-inflammatory peripheral effects. However, there have been no reports about CRF receptor expression and the functional role of CRF in the dendritic cell (DC), which is considered to be the link between allergen uptake and the clinical manifestations of allergic diseases, such as atopic dermatitis. The purpose of this study was to investigate the expression of CRF receptors and the functional role of CRF in the monocyte-derived DC (MoDC) of atopic dermatitis patients and non-atopic healthy controls. In this study, mRNAs for CRF-R1α and 1β, as well as the CRF-R1 protein, were detected in MoDCs. CRF-R2α (but not R2β or R2γ) mRNA and the CRF-R2 protein were present in MoDCs. Exposure of DCs to CRF resulted in a decrease of IL-18 in both atopic dermatitis patients and non-atopic healthy controls. However, CRF did not alter the expression of IL-6, CCL17, CCL18, and CCL22. Therefore, our results demonstrate that CRF could modulate immune responses by acting directly upon DCs. [ABSTRACT FROM AUTHOR]

Background: Although most patients with atopic dermatitis (AD) show high total and allergen-specific serum immunoglobulin E (IgE) levels, a small subgroup of AD patients have normal total IgE levels and negative serum allergen-specific IgE. This subgroup has been termed ‘intrinsic’ AD (IAD) as a counterpart to ‘extrinsic’ AD (EAD). However, the difference of chemokines between IAD and EAD has not yet been evaluated. Objective: We investigated the expression of CC chemokine ligand (CCL) 17, CCL22, and CCL18 in patients with IAD and EAD, which are known to be highly expressed in AD patients. Methods: We assessed the protein levels of these chemokines in peripheral blood mononuclear cells (PBMCs), sera and lesional skins. We also evaluated CCL18 mRNA levels in monocytes, Langerhans cell (LC)-like dendritic cells (DCs) and inflammatory dendritic epidermal cell (IDEC)-like DCs from both types of AD patients. Results: There were no significant differences in CCL17 and CCL22 expression in PBMCs, sera and lesional skins of patients with IAD and EAD. CCL18 expression did not differ in PBMCs, sera and LC-like DCs from the two subgroups, but strong CCL18 expression was observed in lesional skins and IDEC-like DCs in patients with EAD. Lastly, serum CCL18 levels significantly decreased after immunotherapy. Conclusion: This study suggests that the chemokine micromilieu, especially the level of CCL18, is different between EAD and IAD patients. High FcεRI surface-expressing DCs, such as IDEC, were the major source of CCL18, and produced a prominent CCL18 microenvironment in EAD patients compared with IAD patients. [ABSTRACT FROM AUTHOR]