title: IL-1 family cytokines drive Th2 and Th17 cells to innocuous airborne antigens.
abstract: Allergic asthma is commonly thought to result from dysregulated airway inflammatory responses to ubiquitous environmental antigens mediated by CD4(+) T cells polarized to a Th2 or Th17 cell. However, the mechanisms involved in the development of these T-cell responses remain unknown. This study examines the effects of IL-1 family cytokines, such as IL-33 and IL-1β, on the development of antigen-specific Th2 and Th17 cells in the airway. We administered IL-1 family cytokines and model antigens, such as ovalbumin, into the airways of naive BALB/c mice, and examined the cellular and humoral immune responses. To investigate the immunologic mechanisms, we used IL-4 green fluorescent protein reporter mice and mice deficient in the Il4 gene. Innocuous antigens, such as endotoxin-free ovalbumin and short ragweed extract, did not sensitize naive mice when administered through the airways. However, when mice were exposed to the same antigens with IL-1β or IL-33, they developed IgE antibodies. In particular, IL-33 induced robust and long-lasting Th2 cells that produced a large quantity of IL-5 and IL-13 and asthma-like airway pathology. IL-1β induced Th17 cells. In naive, nonsensitized animals, IL-33 stimulated endogenous IL-4 expression by CD4(+) T cells, which was critical for the polarization of CD4(+) T cells to the Th2 type. In the absence of IL-4, mice developed Th17 cells and neutrophilic airway inflammation. In conclusion, IL-1 family cytokines possess a potent adjuvant activity to promote both Th2 and Th17 cells to innocuous airborne antigens, and they may play fundamental roles in the immunopathology of asthma.
authors.affiliation: 1 Department of Medicine and Department of Immunology, Mayo Clinic Rochester, Rochester, Minnesota.
authors.forename: Takao
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Koji
authors.initials: K
authors.lastname: Iijima
authors.forename: James L
authors.initials: JL
authors.lastname: Checkel
authors.forename: Hirohito
authors.initials: H
authors.lastname: Kita
mesh_terms: D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D007156:Immunologic Memory; D007375:Interleukin-1 / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology; D000067596:Interleukin-33; D015847:Interleukin-4 / Q000378:metabolism; D007378:Interleukins / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D057507:Mice, 129 Strain; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D000485:Allergens; D016207:Cytokines; C506536:IL33 protein, human; D007375:Interleukin-1; D053583:Interleukin-1beta; D000067596:Interleukin-33; D007378:Interleukins; D015847:Interleukin-4; D010047:Ovalbumin