Abstract
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.
Highlights
Multiple myeloma (MM), known as plasma cell myeloma, is characterized by excess bone marrow plasma cells, monoclonal paraproteins, bone lytic lesions, renal disease and immunodeficiency [1]
Statistical comparison of the Interferon regulator factor 4 (IRF4) expression levels in the graph showed that significant up-regulation of IRF4 is obvious in 351 MM patients compared with normal plasma cells (NPC) and monoclonal gammopathy of undetermined significance (MGUS) (p < 0.001, Figure 1A)
The results showed that 38 cases of MM patients exhibited a distinct increase of IRF4 expression (+~+ + + +), the positive rate was 65.5% (38/58), including 12 cases (+), 15 cases (+ +), 6 cases (+ + +), 5 cases (+ + + +)
Summary
Multiple myeloma (MM), known as plasma cell myeloma, is characterized by excess bone marrow plasma cells, monoclonal paraproteins, bone lytic lesions, renal disease and immunodeficiency [1]. Interferon regulatory factor (IRF) belongs to the nuclear transcription factors, named by its regulation of interferon [3]. IRF regulates cell response to interferon, and plays a pivotal role in cell proliferation, apoptosis, oncogenic conversion susceptibility and T cell immune responses [3]. Multiple myeloma oncogene 1 (MUM1) / Interferon regulatory factor 4 (IRF4) is one of interferon regulatory factors, which has been shown to be an important transcription factor and is involved in the negative regulation of Th17 cells differentiation and the production of Th17-related cytokines, including IL-17, IL-21 and IL-22 [4, 5]. Mounting evidence support that IRF4 plays a role in the differentiation of Th17 cells
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