Expression profile of IL-33/ST2 and TSLP/TSLP-R in the skin of atopic dermatitis post-allergen exposure

RATIONALE: Barrier-derived cytokines, IL-33 and thymic stromal lymphopoietin (TSLP) are implicated as critical regulators in the pathogenesis of atopic dermatitis (AD). We examined expression of IL-33, TSLP and their cognate receptors (ST-2 and TSLPR, respectively) in skin tissue following an intradermal allergen challenge in patients with AD.

METHODS: Subjects with severe AD and a positive skin prick test to common aeroallergens (n=6) were recruited to this study. Following an 8-day washout for systemic steroids, intradermal challenges with allergen and saline control were performed. Punch biopsies were collected 24 hours later from the challenged areas. Formalin-fixed, paraffin embedded skin biopsies were stained with immunoflourescent labelled antibodies against IL-33, ST2, TSLP &TSLP-R. Images obtained and analysed (NIS-element software) by selecting regions of interest highlighting epidermis and dermis. The thresholding tool was set to pick up positive cells for the above markers and data are represented as positive cells per mm² of the area examined.

RESULTS: At 24 hours post-allergen compared to diluent challenge, there was a significant increase in the cells positive for IL-33 per mm² in the epidermis and dermis (0.34-fold, 1.15-fold, respectively, P<0.05). By comparison, increases in expression of TSLP, ST2 and TSLPR in the epidermis (4.14-fold, 0.38-fold, and 1.37-fold, respectively) and dermis (3.27-fold, 1.46-fold and 0.06-fold, respectively) did not achieve significance likely due to the low sample size.

CONCLUSIONS: Allergen-induced up-regulation of IL-33 expression supports a role for this alarmin in acute inflammation associated with AD.