Late Breaking Abstract - Hypoxia dampens the allergen-dependent adaptive immune response and ameliorates allergic asthma in vivo

Abstract

High altitude therapy has been used to treat allergic asthma with considerable success; the underlying mechanisms however are still insufficiently described. In order to investigate the possible therapeutic effects of sustained reduced oxygen concentrations on allergic asthma, we utilised a new in vivo mouse model in combination with in vitro co-culture systems.

Mice were treated with House Dust Mite (HDM) extract over four weeks and co-exposed to 10% oxygen or room air for the final two weeks. Two weeks of low oxygen treatment was sufficient to strongly downregulate the HDM-induced Th2-response and lung immune cell infiltration. Furthermore, low-oxygen-HDM treated mice displayed reduced symptoms of asthma: airway hyper-responsiveness, mucosal hypersecretion and tissue remodelling were ameliorated compared to normoxic HDM-treated mice.

Additionally, isolated immune cells from mouse and allergic patients were stimulated in vitro under normoxia and hypoxia in different co-culture systems to analyse the adaptive immune response. Hypoxia almost completely suppressed the HDM-induced adaptive immune response in human PBMCs and adaptive responses in mixed-lymphocyte reaction in several murine co-culture models. While hypoxia did not impair effector T-cell responses per-se, it affected APC-differentiation, MHC-II presentation and T-cell cross-talk.

Cumulatively, our results show that hypoxia ameliorates allergic asthma by interfering with the adaptive immune response on several levels. This might help explain the positive effect of high altitude therapy on allergic humans.