Galectin is derived from the combination of galactose and lectin, which can bind to the carbohydrate chain. A number of galectins are localized in various organs, and galectin-7 (Gal-7) is specifically expressed in epidermal keratinocytes. We have previously reported that the extracts from stratum corneum contained high levels of Gal-7 in atopic dermatitis (AD) patients as assessed by proteome analysis. However, issues remain whether Gal-7 is elevated in AD patient sera and how Gal-7 is extracellularly released in epidermal keratinocytes. In this study, we first investigated and found that the serum Gal-7 levels were significantly increased in AD patients (n=25) compared to healthy controls (n=7), and positively correlated with SCORAD, CCL17/TARC, LDH, % eosinophils, TEWL, and VAS of pruritus. We next showed that the intercellular Gal-7 of the prickle layer was strongly positive in AD lesional skin compared to contact dermatitis or normal control by image analysis of immunohistochemical staining. In cultured normal human epidermal keratinocytes (NHEK), we quantified Gal-7 production in the monolayered cells stimulated with or without IFN-, IL-4+IL-13, or IL-17+IL-22 by qPCR and ELISA. Both mRNA and protein levels of Gal-7 were increased in NHEK stimulated with IL-4+IL-13, while IFN- or IL-17+IL-22 stimulation suppressed them after 48 hr. Furthermore, in 3D skin model, IL-4+IL-13 stimulation facilitated the Gal-7 mRNA expression, and promoted Gal-7 accumulation in the intercellular space and stratum corneum of keratinocytes. Taken together, our study demonstrated that Th2 cytokines induce Gal-7 production by epidermal keratinocyte and render them to extracellularly release Gal-7, resulting in elevation of serum levels in AD patients. It is suggested that Gal-7 may play a regulatory role in AD-related inflammation.

High serum and epidermal extracellular levels of galectin-7 in atopic dermatitis