Interleukin-1 alpha controls allergic sensitization to inhaled house dust mite via the epithelial release of GM-CSF and IL-33

House dust mite (HDM) is one of the most common allergens worldwide. In this study, we have addressed the involvement of IL-1 in the interaction between HDM and the innate immune response driven by lung epithelial cells (ECs) and dendritic cells (DCs) that leads to asthma. Mice lacking IL-1R on radioresistant cells, but not hematopoietic cells, failed to mount a Th2 immune response and did not develop asthma to HDM. Experiments performed in vivo and in isolated air-liquid interface cultures of bronchial ECs showed that TLR4 signals induced the release of IL-1 alpha, which then acted in an autocrine manner to trigger the release of DC-attracting chemokines, GM-CSF, and IL-33. Consequently, allergic sensitization to HDM was abolished in vivo when IL-1 alpha, GM-CSF, or IL-33 was neutralized. Thymic stromal lymphopoietin (TSLP) became important only when high doses of allergen were administered. These findings put IL-1 alpha upstream in the cytokine cascade leading to epithelial and DC activation in response to inhaled HDM allergen.