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Role of TSLP in allergen sensitization and allergy elicitation

Thymic stromal lymphopoietin (TSLP) plays an important role in the pathogenesis of asthma so that TSLP receptor knockout (TSLPR−/−) mice are protected from ovalbumin (OVA)‐induced asthma model. However, questions regarding which cells it acts on and when it is needed for the allergic pathogenesis remain to be answered. We demonstrated that a TSLP neutralizing antibody was able to significantly reduce OVA‐induced airway inflammation only when given at both sensitization and challenge phase. Furthermore, TSLPR−/− mice with adoptively transferred wild type dendritic cells (DCs) at either OVA sensitization or challenge showed intermediate levels of eosinophilic airway inflammation and goblet cell metaplasia with no significant airway hyperresponsiveness (AHR). In contrast, the TSLPR−/− mice receiving DCs at both sensitization and challenge showed fully developed eosinophilic airway inflammation, goblet cell metaplasia and AHR similar to wild type animals undergo OVA sensitization and challenge. Taken together, these data suggest that the major target downstream of TSLP is dendritic cells and TSLP acting through DCs is needed for both allergen sensitization and allergy elicitation.