Lauder Sarah N, Tyrrell Victoria J, Allen-Redpath Keith, Aldrovandi Maceler, Gray David, Collins Peter, Jones Simon A, Taylor Philip R, O'Donnell Valerie
Systems Immunity Research Institute, Cardiff University, Cardiff, UK.
Institute of Infection & Immunity, Cardiff University, Cardiff, UK.
Wellcome Open Res. 2017 Jan 4;2:1. doi: 10.12688/wellcomeopenres.10308.1.
. The myeloid enzyme 12/15-lipoxygenase (LOX), which generates bioactive oxidized lipids, has been implicated in numerous inflammatory diseases, with several studies demonstrating an improvement in pathology in mice lacking the enzyme. However, the ability of 12/15-LOX to directly regulate B cell function has not been studied. The influence of 12/15-LOX on B cell phenotype and function, and IgM generation, was compared using wildtype (WT) and 12/15-LOX () deficient mice. The proliferative and functional capacity of splenic CD19 B cells was measured in response to various toll-like receptor agonists. . WT and displayed comparable responses. However , splenic B cell numbers were significantly elevated in mice with a corresponding elevation in titres of total IgM in lung, gut and serum, and lower serum IgM directed against the 12/15-LOX product, 12-hydroxyeicosatetraenoic acid-phosphatidylethanolamine (HETE-PE). Myeloid 12/15-LOX can regulate B cell numbers and innate immune antibody levels , potentially contributing to its ability to regulate inflammatory disease. Furthermore, the alterations seen in 12/15-LOX deficiency likely result from changes in the equilibrium of the immune system that develop from birth. Further studies in disease models are warranted to elucidate the contribution of 12/15-LOX mediated alterations in B cell numbers and innate immune antibody generation to driving inflammation .
髓系酶12/15-脂氧合酶（LOX）可生成具有生物活性的氧化脂质，与多种炎症性疾病有关，多项研究表明缺乏该酶的小鼠病理状况有所改善。然而，12/15-LOX直接调节B细胞功能的能力尚未得到研究。使用野生型（WT）和12/15-LOX（）缺陷小鼠比较了12/15-LOX对B细胞表型和功能以及IgM生成的影响。测量了脾CD19 B细胞对各种Toll样受体激动剂的增殖和功能能力。WT和表现出相当的反应。然而，小鼠脾脏B细胞数量显著增加，肺、肠道和血清中总IgM滴度相应升高，而针对12/15-LOX产物12-羟基二十碳四烯酸-磷脂酰乙醇胺（HETE-PE）的血清IgM降低。髓系12/15-LOX可调节B细胞数量和先天免疫抗体水平，这可能有助于其调节炎症性疾病的能力。此外，12/15-LOX缺乏症中出现的改变可能是由于出生后免疫系统平衡的变化所致。有必要在疾病模型中进行进一步研究，以阐明12/15-LOX介导的B细胞数量改变和先天免疫抗体生成对驱动炎症的作用。
