Background/Purpose: DM (dermatomyositis) is a subtype of inflammatory myopathies，which is a rare autoimmune disease of skeletal muscle.  Although the pathogenic mechanism of DM is still unclear, it was considered as a CD4+T cells driven disease . It was reported that IL-17, a key cytokine of Th17 cells, has been detected in the inflammatory infiltrates of patients with DM. But there is no study focusing on the alteration of Th17 cells in the peripheral blood of patients with DM. In addition to RORC, Kruppel-like factor 4 (KLF4), a transcription factor of cell differentiation, stem cell properties, and malignant transformation, is another positive regulator of Th17 differentiation.

Methods: Thirteen patients with DM were included in this study. The diagnosis was based on commonly accepted clinical and laboratory criteria. Peripheral blood samples were obtained from all patients. The serum concentrations of CK and LDH is by biochemistry test. Healthy subjects were included, ranging from 32 to 50 year old. All of the control subjects were free of a history of DM diseases. All samples were taken in accordance with the regulations and approval of the Affiliated People’s Hospital of Jiangsu University.

Results:

We analyzed the proportion of Th17 cells in PBMCs of DM patients by flow cytometry. The percentage of Th17 cells was significant increased in PBMCs from patients with DM compared with healthy controls. qRT-PCR analysis displays an enhanced expression of IL-17mRNA in the PBMCs from DM patients, with lower expression in healthy controls. To further document the state of Th17 cells in DM patients, we analyzed the expression of RORC mRNA, which plays a considerable role in differentiation of human Th17 cells. As expected, the expression of RORC mRNA in PBMCs from DM patients is significant higher than that from healthy controls. We found that there was a positive correlation between the percentages of Th17 cells and serum level of CK, but not with level of LDH. This result demonstrated that the percentage of Th17 cells could reflect the severity of DM in some extent. In addition, we found that DM patients have significant increased serum concentration of IL-6 and TGF-βin comparison with healthy controls. In addition, serum concentrations of IL-1βis higher in DM patients compared with healthy controls, but this difference did not reach statistical significant.To further analyze the influential factor of Th17 cells enhancement in DM patients, we considered searching the miRNA which may influence the enhancement of Th17 cells. KLF4 is one of the targets of miR-206, and an inverse relationship between miR-206 and KLF4 in human has been confirmed. After acquired the increased expression of KLF4 mRNA in PBMCs of DM patients, we verified the decreased expression of miR-206 in PBMCs and serum of DM patients.

Conclusion: Our data collectively suggest that there is an enhanced frequency of Th17 lymphocytes in DM patients, the augmented expression of KLF4 mRNA may cause by the attenuated expression of miR-206, and the high level of KLF4 mRNA evokes the proportion of Th17 cells in DM patients. And besides the potential role of proinflammatory cytokines, the attenuated expression of miR-206 may regulate the percentage of Th17 cells in DM patients in some extend.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-percentage-of-th17-cells-correlates-with-the-expression-of-microrna-206-in-patients-with-dermatomyositis/