IL-1 family cytokines drive Th2 and Th17 cells to innocuous airborne antigens

Takao Kobayashi, Koji Iijima, James L. Checkel, Hirohito Kita

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Allergic asthma is commonly thought to result from dysregulated airway inflammatory responses to ubiquitous environmental antigens mediated by CD4 + T cells polarizedto 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-1familycytokinesandmodelantigens,suchasovalbumin,intothe 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.

Original languageEnglish (US)
Pages (from-to)989-998
Number of pages10
JournalAmerican journal of respiratory cell and molecular biology
Issue number6
StatePublished - Dec 2013


  • Antigen
  • Asthma
  • IL-1β
  • IL-33

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology


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