Department of Molecular Pneumology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany.
Nephrologische Forschungslaboratorien, Medizinische Klinik m. S. Nephrologie und Internistische Intensivmedizin Charité, Universitätsmedizin Berlin, Berlin, Germany.
Immunology. 2019 Apr;156(4):373-383. doi: 10.1111/imm.13035. Epub 2019 Jan 13.
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.
酸性鞘磷脂酶（ASM）是催化鞘磷脂分解为神经酰胺和磷酸胆碱的酶之一。在本研究中，我们旨在阐明 ASM 在过敏性哮喘中的作用。我们使用卵清蛋白诱导的哮喘小鼠模型，比较了野生型和 ASM 缺陷型小鼠。在野生型小鼠中，急性卵清蛋白模型中支气管肺泡灌洗液中的分泌型 ASM 活性增加，但在耐受模型中则没有。此外，与野生型小鼠相比，在缺乏 ASM 的情况下，血清 IgE 水平降低，而在 ASM 小鼠的肺部观察到间质巨噬细胞和外来抗原诱导的调节性 T 细胞的积累，以及耗尽的 CD4 PD1 T 细胞。总之，在缺乏 ASM 的情况下，我们观察到哮喘中表达 Foxp3 和 CTLA4 的免疫抑制性抗原诱导的调节性 T 细胞以及多核间质巨噬细胞和耗尽的 CD4 PD1 T 细胞的积累与血清 IgE 的抑制有关。
