Kinetics and differential expression of the skin-related chemokines CCL27 and CCL17 in psoriasis, atopic dermatitis and allergic contact dermatitis

Abstract

CCL27 and CCL17 are chemokines believed to be involved in the process of establishing the inflammatory infiltrate, characteristic for the various inflammatory skin diseases. The skinspecific CCL27 binds the chemokine receptor-10 (CCR10), and CCL17 is a chemokine receptor-4 (CCR4) ligand. The purpose of our study was to characterize the expression of CCL27 and CCL17 in the inflammatory skin diseases: psoriasis, atopic dermatitis (AD) and acute allergic contact dermatitis (ACD) induced in nickel-sensitive individuals. Surprisingly, our studies revealed a markedly decreased CCL27 mRNA and protein expression in psoriatic lesions compared with non-lesional psoriatic skin. A minor CCL17 mRNA increase was measured in lesional psoriatic skin. No alterations were found in AD. In ACD, we found a pronounced (90-fold) raise in CCL17 mRNA and a 50-fold increase in CCL17 protein compared with normal skin. A kinetic ACD study of CCL17 expression showed the highest mean value 24 h after hapten application. Furthermore, we found the mRNA levels of CCR10 and CCR4 paralleling the results of their corresponding ligands. Overall, our principal findings were a distinct decrease in CCL27 in lesional psoriatic skin and a marked upregulation of CCL17 in ACD. These findings underscore the differential cutaneous T-cell recruitment in different inflammatory diseases.

CCR10 and its ligands in regulation of epithelial immunity and diseases

“…In fact, while the upregulation of CCL27 and CCL17, a ligand for CCR4, was demonstrated in allergic dermatitis (Homey et al, 2002)(Moed et al, 2004)(Kanda et al, 2005)(Riis et al, 2011a), one recent report found a markedly decreased CCL27 expression in psoriatic lesions compared with non-lesional psoriatic skin and there was only a minor CCL17 mRNA increase in lesional psoriatic skin (Riis et al, 2011a). In addition, the expression of CCR4 was found on CCR10 + lymphocytes in atopic dermatitis skin but not in psoriasis skin (Vestergaard et al, 2003).…”

NOS2 and CCL27: clinical implications for psoriasis and eczema diagnosis and management

“…Although there are hints that CCL27 is crucial for Th2 rather than for Th1-mediated diseases [18,19], its role for eczema as a Th2-dominant disease needs to be elucidated in more detail. However, the authors and others showed that CCL27 is found at lower levels in psoriasis compared with eczema [12,20,21]. Besides, IL17 is supposed to downregulate CCL27 expression [22], and also further cytokines overexpressed in psoriasis, such as INF-g and TNF-a, have a pivotal role in downregulating CCL27 expression at later stages of psoriatic plaques [23].…”

Flexural Eczema Versus Atopic Dermatitis

“…Notably, Kamsteeg et al 57 analyzed patterns of several marker proteins to help differentiate inflammatory skin conditions including psoriasis, atopic dermatitis, allergic contact dermatitis, and irritant contact dermatitis. Through analysis of genetic signatures of skin biopsies via polymerase chain reaction, immunohistochemistry, and bioinformatics, Riis et al 58 found that neuron-specific Nel-like protein 2 exhibited strong induction in atopic dermatitis, whereas CCL17 and CXCL10 mRNA and protein were found in allergic contact dermatitis as compared with control subjects. Differences in expression of fast and slow acetylators of arylamine N-acetyltransferases have been seen between atopic versus allergic contact dermatitis, thus suggesting that N-acetylation polymorphisms could serve as genetic markers for atopic dermatitis.…”