Thymic stromal lymphopoietin and OX40 ligand pathway in the initiation of dendritic cell-mediated allergic inflammation

It was demonstrated 5 years ago that thymic stromal lymphopoietin (TSLP), a IL-7-like cytokine produced by epithelial cells, could strongly activate human myeloid dendritic cells to induce an inflammatory T(H)2 response characterized by high TNF-alpha and little IL-10 production, distinct from the regulatory T(H)2 responses characterized by low TNF-alpha and high IL-10 production. TSLP was found highly expressed by keratinocytes of skin lesions of atopic dermatitis and associated with dendritic cell activation in situ. This suggests for the first time that TSLP represents a master switch of allergic inflammation at the epithelial cell and dendritic cell interface. During the last several years, the evidence for the association of TSLP with human asthma was revealed. The direct link between TSLP expression with the pathogenesis of atopic dermatitis and asthma in vivo was demonstrated. In addition, OX40 ligand was found to be the TSLP-induced molecule on dendritic cells that triggers inflammatory T(H)2 differentiation in the absence of IL-12. TSLP was also demonstrated to direct the innate phase of allergic immune responses through activating mast cells. Therefore, TSLP and OX40 ligand may represent important targets for intervention of the initiation of allergic inflammatory responses.