Immunoregulatory role of acid sphingomyelinase in allergic asthma. Issue 4 (13th January 2019)

• Record Type: Journal Article
• Authors: Sopel, Nina; Kölle, Julia; Dumendiak, Sonja; Koch, Sonja; Reichel, Martin; Rhein, Cosima; Kornhuber, Johannes; Finotto, Susetta
• Is Part Of: Immunology. Volume 156:Issue 4(2019)
• Page Start: 373
• Page End: 383
• Publication Date: 2019-01-13
• Subjects: acid sphingomyelinase -- asthma -- immunosuppression -- macrophages -- regulatory T cells; Immunology -- Periodicals
• DOI: 10.1111/imm.13035
• Languages: English
• ISSNs: 0019-2805

Abstract

Summary: Acid sphingomyelinase (ASM) 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, secretory ASM activity in the bronchoalveolar lavage fluid was increased in the acute ovalbumin model, but not in a tolerogenic model. Furthermore, in the absence of ASM, the serum IgE level was reduced, compared with wild‐type mice, while an accumulation of interstitial macrophages and foreign antigen‐induced regulatory T 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. Abstract : Acid sphingomyelinase (ASM) is one of the enzymes that catalyzes the breakdown of sphingomyelin to ceramide and phosphorylcholine. To elucidate the role of ASM in allergic asthma we used an ovalbumin‐induced murine model of asthma in wild‐type and ASM‐deficient mice. In wild‐type mice, S‐ASM activity was found increased in the bronchoalveolar lavage fluid in the acute ovalbumin model, but not in a tolerogenic model. 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 with fat‐filled lysosomes interstitial macrophages and exhausted CD4 + PD1 + T cells associated with inhibition of serum IgE in asthma.