Targeting psychological stress-steroid-MARCH1 signaling pathway promotes the efficacy of specific allergen immunotherapy.

ABSTRACT

Background: The therapeutic efficacy of allergen specific immunotherapy (SIT) is recognized, but needs improved. Psychological stress influences the immune system's function. The objective of this study is to elucidate the effects of psychological stress on compromising the effectiveness of SIT. Methods: A murine model with the airway allergic disorder (AAD) was established. Mice were treated with SIT with or without restraint stress (Rs). Results: Rs was found to significantly hamper the efficacy of SIT in mice with AAD. Induction of IL-10+ dendritic cells and type 1 regulatory T cells were reduced by Rs in the airway tissues. Rs-induced cortisol release subverted immune tolerance generation. Expression of MARCH1 was elevated in dendritic cells of the allergic lesion sites. The Rs-induced MARCH1 mediated the immune impairment in AAD mice. Genetic ablation of MARCH1 in dendritic cells efficiently blocked the Rs-compromised the therapeutic efficacy of SIT. Conclusion: Rs can increase the expression of MARCH1 in DCs of the allergic lesion sites. MARCH1 interferes with the immune regulatory properties in DCs, and impairs the immune regulatory capacity. Blocking MARCH1 can counteract the Rs-affected SIT efficacy.