The IL-1 receptor 1 is critical for Th2 cell type airway immune responses in a mild but not in a more severe asthma model.
IL-1 alpha and IL-1 beta are potent pro-inflammatory cytokines that regulate many physiological systems by binding and signaling to the same receptor termed IL-1 receptor type 1 (IL-1R1). We have investigated the role of IL-1 for pulmonary immune responses in models of allergic asthma using IL-1R1-deficient (IL-1R1(-/-)) mice. In a model of mild asthma, based on repeated sensitization of mice with low doses of ovalbumin in the absence of any adjuvant and multiple intranasal challenges, the pulmonary eosinophilic inflammation and goblet cell hyperplasia were strongly reduced in IL-1R1(-/-) as compared to control BALB/c mice. Moreover, priming of CD4(+) T cells in bronchial lymph nodes and their recruitment to the lung was affected in IL-1R1(-/-) mice associated with impaired antibody responses including IgG, IgE, and IgA. In contrast, sensitization of mice in the presence of alum adjuvant, a more severe asthma model, rendered the IL-1 pathway dispensable for the development of pulmonary allergic Th2 responses, as eosinophilic inflammation, antibody responses, and CD4(+) T cell priming in lymph nodes were comparable between IL-1R1(-/-) and wild-type mice. These results suggest a critical role of IL-1/IL-1R1 for development of allergic Th2 responses, but its requirement can be overcome by using alum as adjuvant for sensitization.
Schmitz
Nicole
N
Molecular Biomedicine, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland.
Kurrer
Michael
M
Kopf
Manfred
M
D000818:Animals; D001249:Asthma / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement; D007136:Immunoglobulins / Q000096:biosynthesis; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011657:Pulmonary Eosinophilia / Q000276:immunology; D017472:Receptors, Interleukin-1 / Q000502:physiology*; D053573:Receptors, Interleukin-1 Type I; D018418:Th2 Cells / Q000276:immunology*
D007136:Immunoglobulins; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I