Skin-specific overexpression of TSLP resulted in an AD-like phenotype, with the development of eczematous lesions containing inflammatory dermal cellular infiltrates, a dramatic increase in Th2 CD4+ T cells expressing cutaneous homing receptors, and elevated serum levels of IgE.
We show here that topical application of the physiologically active ligand [1alpha,25-(OH)(2)D(3); calcitriol] of the vitamin D receptor, or of its low-calcemic analog MC903 (calcipotriol; Dovonex), induces TSLP expression in epidermal keratinocytes, which results in an atopic dermatitis-like syndrome mimicking that seen in RXRalphabeta(ep-/-) mutants and transgenic mice overexpressing TSLP in keratinocytes.
We show here that topical application of the physiologically active ligand [1alpha,25-(OH)(2)D(3); calcitriol] of the vitamin D receptor, or of its low-calcemic analog MC903 (calcipotriol; Dovonex), induces TSLP expression in epidermal keratinocytes, which results in an atopic dermatitis-like syndrome mimicking that seen in RXRalphabeta(ep-/-) mutants and transgenic mice overexpressing TSLP in keratinocytes.
Compelling evidence suggests that the epithelial cell-derived cytokine thymic stromal lymphopoietin (TSLP) may initiate asthma or atopic dermatitis through a dendritic cell-mediated T helper (Th)2 response.
The epithelial-derived cytokine thymic stromal lymphopoietin (TSLP) is sufficient to induce asthma or atopic dermatitis-like phenotypes when selectively overexpressed in transgenic mice, or when driven by topical application of vitamin D3 or low-calcemic analogues.
The review also dissects, based on information from mouse models of AD, the contributions of the innate and adaptive immune system to the pathogenesis of AD, including the effect of mechanical skin injury on the polarization of skin dendritic cells, mediated by keratinocyte-derived cytokines such as thymic stromal lymphopoietin (TSLP), IL-6, and IL-1, that results in a Th2-dominated immune response with a Th17 component in acute AD skin lesions and the progressive conversion to a Th1-dominated response in chronic AD skin lesions.
This role is supported by the finding that TSLP expression is upregulated in keratinocytes of atopic dermatitis skin lesions and in bronchial epithelial cells in asthma.
Thymic stromal lymphopoietin (TSLP) plays a pivotal role in allergic diseases such as atopic dermatitis, asthma, and chronic obstructive pulmonary disease.
In support of genetic analyses, exaggerated TSLP production is associated with asthma, atopic dermatitis and food allergies in patients, and studies in murine systems demonstrated that TSLP promotes T(H)2 cytokine-mediated immunity and inflammation.
We also assessed the effect of 2,4-dinitrofluorobenzene on TSLP and the TH2 response in mice in which the inflammasome and IL-1 signaling pathways were blocked, either genetically or pharmacologically, in 2 models of AD.
The modulation by LL-37 of the keratinocyte proinflammatory responses induced by cytokine milieus and dsRNA suggests novel roles for LL-37 in skin inflammation such as the promotion of IL17/IL-22/IL-6-associated psoriasis and suppression of TSLP-associated atopic dermatitis.
In this study, we identified a positive association between interleukin-9 (IL-9) and TSLP concentration in the serum of infants with atopic dermatitis.
Thymic stromal lymphopoietin (TSLP) may have a key role in the initiation and maintenance of allergic inflammatory diseases, including atopic dermatitis.
The aim of this study was to examine the relationships between the degree of TSLP expression in the skin and the severity of AD, eruption type and epidermal barrier function using a non-invasive method in a sizeable group of the patients.