Aberrant NLRP3 inflammasome associated with aryl hydrocarbon receptor potentially contributes to the imbalance of T-helper cells in patients with acute myeloid leukemia.
Aberrant NLRP3 inflammasome associated with aryl hydrocarbon receptor potentially contributes to the imbalance of T-helper cells in patients with acute myeloid leukemia.
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与芳基碳氢化合物受体相关的异常 NLRP3 免疫小体可能导致急性髓系白血病患者 T 辅助细胞失衡
DOI：
10.3892/ol.2017.7177
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发表时间：
2017-12
期刊：
影响因子：
2.9
通讯作者：
Ma D
中科院分区：
文献类型：
--
作者：
Jia Y;Zhang C;Hua M;Wang M;Chen P;Ma D
急性髓系白血病(AML)是一种血液系统恶性肿瘤，免疫反应在其进展中起着关键作用。芳香烃受体(AHR)参与免疫系统的调节，特别是T辅助细胞(Th)亚群的分化。尽管NLRP3家族的炎性小体在自身免疫性和炎症性疾病的发病机制中起重要作用，但它在急性髓系白血病的发生发展中的作用尚不清楚。因此，为了确定和描述AHR和NLRP3炎症体在AML发病机制中的可能作用及其与Th亚群(Th1、Th22)的关系，本研究检测了AHR和NLRP3炎症体分子在AML患者外周血和骨髓中的表达水平。用双抗体夹心法测定外周血中IL-18的浓度，以及Th22和Th1的比例。在本研究中，有三组患者：新诊断(ND)患者、完全缓解(CR)患者和正常对照组。新诊断(ND)患者的骨髓单个核细胞(BMMCs)中NLRP3炎症体分子的表达明显高于完全缓解(CR)患者。NLRP3炎症体分子在外周血单个核细胞(PBMC)中也有异常表达，并伴有外周血中IL-18的异常水平。初治AML患者达到CR后，IL-18mRNA相对水平恢复正常。骨髓AHR在ND患者中的表达明显高于CR患者。此外，AML患者NLRP3炎性小体分子的表达水平与AHR的表达水平显著相关。在Th亚群中，ND患者外周血中Th22的比例明显高于CR患者或对照组，并伴有Th1的降低。结论：AHR相关的NLRP3炎性小体参与了AML的发生发展，并可能影响Th亚群的分化。
Acute myeloid leukemia (AML) is a hematological malignancy in which the immune response serves a pivotal role in progression. Aryl hydrocarbon receptor (AHR) is involved in the modulation of the immune system, particularly in the differentiation of T-helper cell (Th) subsets. Although the NLR family pyrin domain-containing 3 (NLRP3) inflammasome has been implicated as essential in the pathogenesis of autoimmune and inflammatory diseases, the role it serves in the development of AML remains unknown. Therefore, in order to identify and describe the possible roles of AHR, as well as NLRP3 inflammasome, in the pathogenesis of AML and their relationship with Th subsets (Th1 Th22), the present study investigated the mRNA expression levels of AHR and NLRP3 inflammasome molecules in the peripheral blood and bone marrow. Concentrations of plasma IL-18 were also investigated in peripheral blood by ELISA, as well as the proportions of Th22 and Th1. In the present study, there were three groups: Newly diagnosed (ND) patients; complete remission (CR); and normal controls. A markedly increased expression of NLRP3 inflammasome molecules in bone marrow mononuclear cells (BMMCs) from newly diagnosed (ND) patients compared with patients in complete remission (CR) was identified. NLRP3 inflammasome molecules were also observed to be aberrantly expressed in peripheral blood (PB) mononuclear cells (PBMCs), accompanied with aberrant interleukin (IL)-18 levels in PB plasma. The relative level of IL-18 mRNA became normal after the ND patients with AML achieved CR. In bone marrow, the expression of AHR was significantly higher in ND patients than in CR patients. Furthermore, the expression level of NLRP3 inflammasome molecules was significantly correlated with AHR expression in patients with AML. In the Th subsets, a significantly increased proportion of Th22 in PB from ND patients compared with CR patients or controls was identified, accompanied with decreased Th1. It was concluded that the NLRP3 inflammasome, associated with AHR, was involved in the development of AML and may have influenced the differentiation of Th subsets.
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影响因子：
6.1
作者：
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通讯作者：
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影响因子：
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