Human epithelial cells trigger dendritic cell-mediated allergic inflammation by producing TSLP

Human epithelial cells trigger dendritic cell-mediated allergic inflammation by producing TSLP

| Vassili Soumelis', Pedro A. Reche', Holger Kanzler', Wei Yuan', Gina Edward', Bernhart Homey'1,2, Michel Gilliet', Steve Ho', Svetlana Antonenko', Annti Lauerman3, Kathleen Smith', Daniel Gorman', Sandra Zurawski', Jon Abrams', Satish Menon', Terri McClanahan', Rene de Waal-Malefyt', Fernando Bazan', Robert A. Kastelein' and Yong-Jun Liu'
Human epithelial cells trigger dendritic cell-mediated allergic inflammation by producing TSLP. The study shows that human thymic stromal lymphopoietin (TSLP) potently activates CD11c+ dendritic cells (DCs) and induces the production of T helper 2 (Th2)-attracting chemokines TARC and MDC. TSLP-activated DCs prime naive T cells to produce proallergic cytokines such as IL-4, IL-5, IL-13, and TNF-α, while downregulating IL-10 and IFN-γ. TSLP is highly expressed by epithelial cells, especially keratinocytes in atopic dermatitis. TSLP expression is associated with Langerhans cell migration and activation in situ. These findings highlight the role of TSLP in initiating allergic inflammation. Allergic diseases affect about 20% of the population in Western countries, including asthma, allergic rhinitis, atopic dermatitis, and food allergy. Allergic inflammation results from a complex immunological cascade leading to dysregulated production of Th2-derived cytokines such as IL-4, IL-5, and IL-13, which trigger IgE production, eosinophilia, and mucus production. Dendritic cells (DCs), professional antigen-presenting cells, play a key role in the pathogenesis of allergic diseases. However, the initial signal that primes DCs to induce T cells to produce proallergic Th2 cytokines is unknown. Epithelial cells, located at sites of allergen entry, interact closely with DCs in situ. However, it is not known whether DCs play a role in triggering the allergic immune cascade. Thymic stromal lymphopoietin (TSLP) is an IL-7-like cytokine that activates CD11c+ DCs but does not have direct effects on B cells, T cells, NK cells, neutrophils, or mast cells. Human TSLP activates CD11c+ DCs, which subsequently prime naive T cells to produce high concentrations of IL-13, IL-5, and TNF-α, moderate amounts of IL-4, and downregulate IL-10 and IFN-γ. TSLP is highly expressed by epithelial cells in inflamed tonsils and keratinocytes in atopic dermatitis. Thus, TSLP represents a key epithelial cell or keratinocyte-derived cytokine that directly triggers DC-mediated allergic inflammation. TSLP potently activates human CD11c+ DCs, which subsequently prime naive CD4+ T cells to produce high concentrations of IL-13, IL-5, and TNF-α, moderate amounts of IL-4, and downregulate IL-10 and IFN-γ. TSLP-DCHuman epithelial cells trigger dendritic cell-mediated allergic inflammation by producing TSLP. The study shows that human thymic stromal lymphopoietin (TSLP) potently activates CD11c+ dendritic cells (DCs) and induces the production of T helper 2 (Th2)-attracting chemokines TARC and MDC. TSLP-activated DCs prime naive T cells to produce proallergic cytokines such as IL-4, IL-5, IL-13, and TNF-α, while downregulating IL-10 and IFN-γ. TSLP is highly expressed by epithelial cells, especially keratinocytes in atopic dermatitis. TSLP expression is associated with Langerhans cell migration and activation in situ. These findings highlight the role of TSLP in initiating allergic inflammation. Allergic diseases affect about 20% of the population in Western countries, including asthma, allergic rhinitis, atopic dermatitis, and food allergy. Allergic inflammation results from a complex immunological cascade leading to dysregulated production of Th2-derived cytokines such as IL-4, IL-5, and IL-13, which trigger IgE production, eosinophilia, and mucus production. Dendritic cells (DCs), professional antigen-presenting cells, play a key role in the pathogenesis of allergic diseases. However, the initial signal that primes DCs to induce T cells to produce proallergic Th2 cytokines is unknown. Epithelial cells, located at sites of allergen entry, interact closely with DCs in situ. However, it is not known whether DCs play a role in triggering the allergic immune cascade. Thymic stromal lymphopoietin (TSLP) is an IL-7-like cytokine that activates CD11c+ DCs but does not have direct effects on B cells, T cells, NK cells, neutrophils, or mast cells. Human TSLP activates CD11c+ DCs, which subsequently prime naive T cells to produce high concentrations of IL-13, IL-5, and TNF-α, moderate amounts of IL-4, and downregulate IL-10 and IFN-γ. TSLP is highly expressed by epithelial cells in inflamed tonsils and keratinocytes in atopic dermatitis. Thus, TSLP represents a key epithelial cell or keratinocyte-derived cytokine that directly triggers DC-mediated allergic inflammation. TSLP potently activates human CD11c+ DCs, which subsequently prime naive CD4+ T cells to produce high concentrations of IL-13, IL-5, and TNF-α, moderate amounts of IL-4, and downregulate IL-10 and IFN-γ. TSLP-DC
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Understanding Human epithelial cells trigger dendritic cell%E2%80%93mediated allergic inflammation by producing TSLP