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

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.