Low oxygen levels decrease adaptive immune responses and ameliorate experimental asthma in mice

Allergy. 2022 Mar;77(3):870-882. doi: 10.1111/all.15020. Epub 2021 Aug 1.


Background: High-altitude therapy has been used as add-on treatment for allergic asthma with considerable success. However, the underlying mechanisms remain unclear. In order to investigate the possible therapeutic effects of high-altitude therapy on allergic asthma, we utilized a new in vivo mouse model.

Methods: Mice were treated with house dust mite (HDM) extract over 4 weeks and co-exposed to 10% oxygen (Hyp) or room air for the final 2 weeks. Experimental asthma was assessed by airway hyper-responsiveness, mucus hypersecretion and inflammatory cell recruitment. Isolated immune cells from mouse and allergic patients were stimulated in vitro with HDM under Hyp and normoxia in different co-culture systems to analyse the adaptive immune response.

Results: Compared to HDM-treated mice in room air, HDM-treated Hyp-mice displayed ameliorated mucosal hypersecretion and airway hyper-responsiveness. The attenuated asthma phenotype was associated with strongly reduced activation of antigen-presenting cells (APCs), effector cell infiltration and cytokine secretion. In vitro, hypoxia almost completely suppressed the HDM-induced adaptive immune response in both mouse and human immune cells. While hypoxia did not affect effector T-cell responses per-se, it interfered with antigen-presenting cell (APC) differentiation and APC/effector cell crosstalk.

Conclusions: Hypoxia-induced reduction in the Th2-response to HDM ameliorates allergic asthma in vivo. Hypoxia interferes with APC/T-cell crosstalk and confers an unresponsive phenotype to APCs.

Keywords: MHC-II; allergy; asthma; dendritic cells; hypoxia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens
  • Animals
  • Asthma*
  • Disease Models, Animal
  • Humans
  • Hypoxia
  • Immunity, Humoral
  • Mice
  • Oxygen* / pharmacology
  • Pyroglyphidae
  • Th2 Cells


  • Allergens
  • Oxygen