Aberrant NLRP3 inflammasome associated with aryl hydrocarbon receptor potentially contributes to the imbalance of T‑helper cells in patients with acute myeloid leukemia

Jia,Yan; Zhang,Chen; Hua,Mingqiang; Wang,Min; Chen,Ping; Ma,Daoxin

doi:10.3892/ol.2017.7177

Aberrant NLRP3 inflammasome associated with aryl hydrocarbon receptor potentially contributes to the imbalance of T‑helper cells in patients with acute myeloid leukemia

Authors:
- Yan Jia
- Chen Zhang
- Mingqiang Hua
- Min Wang
- Ping Chen
- Daoxin Ma
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Affiliations: Department of Hematology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China, Department of Hematology, Jinan Central Hospital, Shandong University, Jinan, Shandong 250013, P.R. China
Published online on: October 12, 2017 https://doi.org/10.3892/ol.2017.7177
Pages: 7031-7044
Copyright: © Jia et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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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