Immunoregulatory role of ASM in allergic asthma.

Acid sphingomyelinase is one of the enzymes that catalyzes the breakdown of sphingomyelin to ceramide and phosphorylcholine. In this study, we aimed at elucidating the role of ASM in allergic asthma. We used an Ovalbumin-induced murine model of asthma where we compared wild type and ASM-deficient mice. In wild type mice, S-ASM activity in the bronchoalveolar lavage fluid (BALF) was found increased in the acute OVA-model, but not in a tolerogenic model. Furthermore, in the absence of ASM, the serum IgE level was found reduced, as compared to wild type mice, while an accumulation of interstitial macrophages and foreign antigen induced T regulatory cells along with exhausted CD4+ PD1+ T cells was observed in the lungs of ASM-/- mice. In conclusion, in the absence of ASM, we observed an accumulation of immunosuppressive antigen induced regulatory T cells expressing Foxp3 and CTLA4 in the lung as well as multinucleated interstitial macrophages and exhausted CD4+ PD1+ T cells associated with inhibition of serum IgE in asthma. This article is protected by copyright. All rights reserved.