Interleukin-1α 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-1α, 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-1α, 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-1α upstream in the cytokine cascade leading to epithelial and DC activation in response to inhaled HDM allergen.
Laboratory of Immunoregulation and Mucosal Immunology, Ghent University, 9000 Ghent, Belgium.
Monique A M
MA
Willart
Kim
K
Deswarte
Philippe
P
Pouliot
Harald
H
Braun
Rudi
R
Beyaert
Bart N
BN
Lambrecht
Hamida
H
Hammad
D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology; D053582:Interleukin-1alpha / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology; D000067596:Interleukin-33; D007378:Interleukins / Q000276:immunology*; D008168:Lung / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D039981:Pyroglyphidae / Q000276:immunology*; D020545:Respiratory Mucosa / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology; D000094632:Thymic Stromal Lymphopoietin
D000485:Allergens; D016207:Cytokines; C506535:Il33 protein, mouse; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D000067596:Interleukin-33; D007378:Interleukins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000094632:Thymic Stromal Lymphopoietin