Postgraduate Medical School, University of Chieti, Chieti, Italy.
Medicine and Surgery Department, Centre of Neuroscience of Milan, University of Milan-Bicocca, Italy.
Eur J Pharmacol. 2019 Sep 5;858:172473. doi: 10.1016/j.ejphar.2019.172473. Epub 2019 Jun 19.
Systemic mastocytosis in various forms is characterized by mast cell (MC) infiltration of the bone marrow and other internal organs. The most common form is the indolent one with life expectancy similar to the normal population, while the systemic aggressive myeloproliferative type presents serious damage to various organs and is associated with mature and immature atypical mast cells. In systemic mastocytosis patients, MCs could be activated with consequent severe anaphylactic reactions, along with other symptoms. MCs, which are reactive to a variety of external factors such as allergens or other inflammatory or physical stimuli, derive from pluripotent cellular progenitor CD34 which leaves the bone marrow as CD34/CD17 for implantation in the tissues where they reach maturation. MCs participate in the innate and adaptive immune system where they play a role in host defense. Activation of MCs occurs through the binding of IgE to FcεRI receptor, and initiates the phosphorylation and activation of the p38 tyrosine MAP kinase. After various reactions there is a subsequent translation and generation of pro-inflammatory cytokines which are strongly linked to allergic inflammation and mastocytosis. Human cytokine interleukin-37 (IL-37), a unique IL-1β family member, has strong protective and anti-inflammatory properties, influencing cellular metabolism. We investigated the effect of IL-37 on inflammation in mastocytosis and report that the hematopoietic expression of IL-37 can reduce the inflammatory state in this disease. IL-37 limits excessive inflammation, which suggests that IL-37 may be beneficial to the metabolic and inflammatory process and is a candidate as a potential new therapeutic agent.
各种形式的系统性肥大细胞增多症的特征是骨髓和其他内脏器官中有肥大细胞（MC）浸润。最常见的形式是惰性的，其预期寿命与正常人群相似，而系统性侵袭性骨髓增生性类型则对各种器官造成严重损害，并与成熟和不成熟的非典型肥大细胞有关。在系统性肥大细胞增多症患者中，MC 可能被激活，导致严重的过敏反应以及其他症状。MC 对过敏原或其他炎症或物理刺激等多种外部因素有反应，源自多能细胞祖细胞 CD34，它离开骨髓作为 CD34/CD17 植入到它们达到成熟的组织中。MC 参与先天和适应性免疫系统，在宿主防御中发挥作用。MC 的激活是通过 IgE 与 FcεRI 受体结合来实现的，从而启动 p38 酪氨酸 MAP 激酶的磷酸化和激活。经过各种反应，随后会翻译并产生促炎细胞因子，这些细胞因子与过敏炎症和肥大细胞增多症密切相关。人类细胞因子白细胞介素-37（IL-37）是一种独特的 IL-1β 家族成员，具有强大的保护和抗炎特性，影响细胞代谢。我们研究了 IL-37 对肥大细胞中炎症的影响，并报告造血细胞表达的 IL-37 可以减轻这种疾病的炎症状态。IL-37 限制过度炎症，这表明 IL-37 可能对代谢和炎症过程有益，是一种有前途的新治疗药物候选物。
