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Please cite this paper as: CC chemokines as potential immunologic markers correlated with clinical improvement of atopic dermatitis patients by immunotherapy. Experimental Dermatology 2010; 19: 246–251. Although immunotherapy is not accepted as a curative treatment for atopic dermatitis (AD), most studies have shown positive effects of immunotherapy on AD patients. The serum levels of CC chemokine ligand 17 (CCL17), CCL22 and CCL18 have been reported to be highly correlated with disease severity, which suggests important roles for CC chemokines in the pathogenesis of AD. Objective: The purpose of this study was to investigate the changes in clinical and immunologic markers before and after immunotherapy and to find which CC chemokines correlate with clinical improvement after immunotherapy with house dust mite (HDM) allergens in AD patients. Methods and Results: A total of 20 AD patients who were sensitized to HDM allergens through a skin-prick test and Pharmacia CAP system were treated with subcutaneous immunotherapy using HDM allergens (treatment duration 12–60 months). Eczema area and severity index scores in 20 patients with AD decreased significantly after immunotherapy ( P < 0.001). Serum total immunoglobulin E (IgE) and Dermatophagoides pteronyssinus-specific IgE levels tended to decrease after treatment although this was not statistically significant, and the D. farinae-specific IgE level showed no change. Serum CCL17, CCL22 and CCL18 levels decreased significantly from baseline after treatment ( P = 0.043, 0.017 and <0.001, respectively). The percentage reductions in serum CCL17 and CCL22 level were significantly correlated with reductions in disease severity ( P = 0.007, R2 = 0.301 and P = 0.037, R2 = 0.177, respectively). Conclusion: We suggest that CCL17 and CCL22 are good immunological marker candidates that can be used to assess clinical improvement after immunotherapy in AD patients. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic IL-23/Th17 pathway-associated skin disease. An increased expression of lesional CCL20 can recruit CCR6+ Th17, and lesional cytokine milieu persistently activates keratinocytes to produce CCL20. Lipid-lowering drugs, statins, are known to possess immune-modulating functions. In this study, we explored an inhibitory effect of statins on CCL20/CCR6 interaction. We demonstrated that IL-1β, TNF-α, and IL-17A significantly increased CCL20 production from HaCaT cells. However, these increments were markedly inhibited by fluvastatin and simvastatin, but not by pravastatin. In the chemotaxis migration assay, pretreatment with fluvastatin and simvastatin inhibited the migration of human CD4+ T cells towards CCL20. However, the level of CCR6 surface expression in memory CD4+ T cells was not affected. Our results suggest that not all, but specific types of statins may be of benefit in alleviating psoriasis partially via interrupting CCL20/CCR6 chemotactic interaction, the mechanism which may eventually lessen the infiltration of Th17 cells. [ABSTRACT FROM AUTHOR]

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]