Thymic stromal lymphopoietin converts human epidermal Langerhans cells into antigen-presenting cells that induce proallergic T cells

BackgroundThymic stromal lymphopoietin (TSLP) endows human CD11c+ dendritic cells (DCs) from peripheral blood with the capacity to induce proallergic T cells. TSLP is present at high levels in the epidermis of atopic dermatitis where it appears to trigger emigration of epidermal Langerhans cells (LCs); however, nothing else is known about the influence of TSLP on LCs.ObjectiveEffects of TSLP on human epidermal LCs were investigated.MethodsLCs were isolated by trypsinization from healthy human skin, highly enriched by immunomagnetic techniques (via CD1a) and cultured for 2 days. Additionally, migratory LCs were obtained by emigration from epidermal sheets for 3 days.ResultsThe addition of TSLP promoted survival and maturation of LCs obtained by trypsinization, as indicated by their increased expression of CD83, CD86, and high levels of MHC II. TSLP markedly increased numbers of migratory LCs. Allogeneic naïve CD4+ T cells, cocultured with migratory TSLP-LCs produced less IFN-γ and IL-10 and more IL-4, IL-5, IL-13, and TNF-α. Finally, TSLP-LCs secreted markedly more of the TH2 T-cell–attracting chemokine CCL17/thymus and activation-regulated chemokine.ConclusionThese cytokine patterns correspond to those described for TSLP-treated blood DCs. They highlight a direct effect of TSLP on epidermal LCs.Clinical implicationsOur data emphasize a critical role for LCs in the triggering of atopic dermatitis. Furthermore, they underscore the interest in TSLP as a potential therapeutic target in atopic diseases.