Bai Hua, Wu Shuang, Wang Rong, Xu Ji, Chen Lijuan
Department of Hematology, First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.
Oncotarget. 2017 Aug 3;8(49):85392-85400. doi: 10.18632/oncotarget.19907. eCollection 2017 Oct 17.
Interferon regulator factor 4 (IRF4) is characterized to be a member of interferon regulatory family, which is predominantly expressed in bone marrow plasma cells of patients with multiple myeloma (MM). Recent studies indicated IRF4 is critical for T-help cells (Th17) differentiation and interleukin-17 (IL-17) secretion. Here, a total of 58 MM patients were enrolled in this study, the proportions of Th17 cells and T regulatory (Treg) cells in peripheral blood mononuclear cells (PBMCs) were determined by flow cytometric analysis. Immunohistochemistry was employed to detect the IRF4 expression in bone marrow. Herein, we observed a significant increase of IRF4 in bone marrow accompanied with a notable up-regulation of Th17 cells in PBMC within MM patients compared with healthy donors. Furthermore, the proportions of Th17 cells and serum IL-17 levels were higher in patients with stage III than stage I & II MM patients, and those parameters were positively correlated with the expression of IRF4 in these cases. These results for the first time indicate that a crosstalk between IRF4 and Th17 cells is associated with MM prognosis, and IRF4 may be served an important target for MM immunotherapy.
干扰素调节因子4(IRF4)是干扰素调节因子家族的一员,主要在多发性骨髓瘤(MM)患者的骨髓浆细胞中表达。最近的研究表明,IRF4对辅助性T细胞(Th17)分化和白细胞介素-17(IL-17)分泌至关重要。本研究共纳入58例MM患者,采用流式细胞术分析外周血单个核细胞(PBMC)中Th17细胞和调节性T细胞(Treg)细胞比例。采用免疫组织化学法检测骨髓中IRF4的表达。在此,我们观察到与健康供体相比,MM患者骨髓中IRF4显著增加,同时PBMC中Th17细胞显著上调。此外,III期MM患者的Th17细胞比例和血清IL-17水平高于I期和II期MM患者,且这些参数与IRF4在这些病例中的表达呈正相关。这些结果首次表明,IRF4与Th17细胞之间的相互作用与MM预后相关,IRF4可能是MM免疫治疗的重要靶点。