Interleukin-37 reduces inflammation and impairs phagocytosis of platelets in immune thrombocytopenia (ITP)
Interleukin-37 reduces inflammation and impairs phagocytosis of platelets in immune thrombocytopenia (ITP)
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Interleukin-37 可减轻免疫性血小板减少症 (ITP) 患者的炎症并损害血小板的吞噬作用
DOI：
10.1016/j.cyto.2019.154853
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发表时间：
2020
期刊：
影响因子：
3.8
通讯作者：
Li Guosheng
中科院分区：
文献类型：
--
作者：
Zhao Yajing;Ni Xiaofei;Xu Pengcheng;Liu Qiang;Sun Tao;Liu Xinguang;Ji Xuebin;Qiu Jihua;Li Ju;Wang Shuang;Han Panpan;Peng Jun;Hou Ming;Li Guosheng
免疫性血小板减少症（ITP）是一种自身免疫性疾病，其特征是血小板计数低，伴有异质性出血表现。ITP的严重出血与血小板计数降低不完全相关。Fcγ受体（FcγR）介导的血小板破坏是ITP的主要机制之一。白细胞介素-37（IL-37）是多种自身免疫性疾病中先天免疫和炎症反应的基本天然抑制剂。然而，IL-37在ITP发病机制中的作用尚不清楚。在本研究中，我们发现IL-37在ITP患者中表达升高，并且与ITP患者的血小板计数和出血严重程度相关，表明IL-37可以作为评估ITP疾病严重程度的候选指标。在体外研究中，IL-37通过下调MAPK、AKT和NF-κB信号通路的磷酸化而对ITP患者的单核/巨噬细胞产生抗炎作用。此外，IL-37恢复激活和抑制Fcγ R的平衡，并降低单核细胞/巨噬细胞对抗体介导的血小板吞噬作用。我们的研究结果表明，IL-37可能是疾病严重程度的一个有希望的指标，补充IL-37可能对ITP患者有治疗益处。
Immune thrombocytopenia (ITP) is an autoimmune disease characterized by low platelet count with heterogeneous bleeding manifestations. Severe bleeding in ITP is not completely related with low platelet count. Fcγ receptor (FcγR)-mediated platelet destruction is one of the major mechanisms of ITP. Interleukin-37 (IL-37) is a fundamental natural suppressor of innate immunity and inflammatory responses in several autoimmune diseases. However, the role of IL-37 in the pathogenesis of ITP is unknown. In the present study, we identified that IL-37 expression was elevated in ITP patients, which was correlated with platelet count and the severity of bleeding in ITP, indicating that IL-37 could be a candidate in evaluating disease severity of ITP. In thein vitrostudy, IL-37 initiated an anti-inflammatory effect on monocytes/macrophages from ITP patients by down-regulating the phosphorylation of MAPK, AKT, and NF-κB signaling pathways. Moreover, IL-37 restored the balance of activating and inhibitory FcγRs and decreased antibody-mediated platelet phagocytosis by monocytes/macrophages. Our findings suggest that IL-37 may be a promising indicator of the disease severity and supplementation of IL-37 may be therapeutically beneficial for ITP patients.