ABSTRACT
Thymic stromal lymphopoietin (TSLP) plays an important role in allergic diseases and is highly expressed in keratinocytes in human lesional atopic dermatitis (AD) skin. In nonlesional AD skin TSLP expression can be induced by applying house dust mite allergen onto the skin in the atopy patch test. Several studies have demonstrated that the induction of TSLP expression in mouse skin does not only lead to AD-like inflammation of the skin, but also predisposes to severe inflammation of the airways. In mice, TSLP expression can be induced by application of the 1,25-dihydroxyvitamin D3 (VD3) analogue calcipotriol and results in the development of eczema-like lesions. The objective is to investigate the effect of VD3 (calcitriol) or calcipotriol on TSLP expression in normal human skin and skin from AD patients. Using multiple ex vivo experimental setups, the effects of calci(po)triol on TSLP expression by normal human skin, and skin from AD patients were investigated and compared to effects of calcipotriol on mouse and non-human primates (NHP) skin. No induction of TSLP expression (mRNA or protein) was observed in human keratinocytes, normal human skin, nonlesional AD skin, or NHP skin samples after stimulation with calcipotriol or topical application of calcitriol. The biological activity of calci(po)triol in human skin samples was demonstrated by the increased expression of the VD3-responsive Cyp24a1 gene. TSLP expression was induced by cytokines (IL-4, IL-13, and TNF-α) in skin samples from all three species. In contrast to the findings in human and NHP, a consistent increase in TSLP expression was confirmed in mouse skin biopsies after stimulation with calcipotriol. VD3 failed to induce expression of TSLP in human or monkey skin in contrast to mouse, implicating careful extrapolation of this often-used mouse model to AD patients.
ABSTRACT
BACKGROUND: Serum thymus and activation-regulated chemokine (sTARC) levels reflect disease severity of atopic dermatitis (AD) in small study populations. It remains unclear whether sTARC is a reliable outcome measurement for AD severity in heterogeneous AD populations in daily practice. OBJECTIVE: We sought to assess the utility of sTARC as a biomarker for monitoring AD severity in adults in daily practice. METHODS: sTARC, clinical skin score (Six Area, Six Sign AD [SASSAD]), and body surface area measurements were collected from all adult patients with AD visiting our clinic between March 2009 and March 2012, at first visit or exacerbation (baseline). In addition, data from short-term and long-term follow-up visits were collected. RESULTS: At baseline sTARC levels ranged widely (n = 320; minimum-maximum: 3-50,400 pg/mL) and sTARC and SASSAD or body surface area correlated moderately. In the majority of patients, sTARC and SASSAD or body surface area changed congruently during follow-up. LIMITATIONS: Data were collected retrospectively. CONCLUSION: sTARC may represent a suitable biomarker for monitoring of AD severity in daily practice.
