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Study on the role of microRNA in the function of Treg-of-B cells
Regulatory T cells,Treg-of-B cells,microRNA,microRNA-210,microRNA-155,
|Publication Year :||2019|
小分子核糖核酸 (microRNA) 為片段長約22至25個核苷酸，具有調控功能的非編碼核糖核酸分子。由DNA序列轉錄而來的microRNA，會經由不同酵素的切割，使最後成熟的microRNA為單股序列，在細胞質中與RNA誘導沉默複合體 (RISC) 結合，進而執行其基因調控的功能。成熟的單股microRNA利用和目標基因相互配對的程度，進而達到抑制轉譯進行，或是以基因降解的方式執行其調控基因的功能。
In our previous studies, we found that splenic B cells could induce naïve CD4+CD25- T cells into CD4+CD25+Foxp3- regulatory T cells in a cell-cell contact manner, termed Treg-of-B cells. Treg-of-B cells could express regulation-related surface markers and secrete regulatory cytokine. Unlike natural regulatory T cells, Treg-of-B cells did not express Foxp3, but they could also exert the suppressive function like Foxp3+ natural regulatory T cells. In addition, several studies revealed that Treg-of-B cells could alleviate some inflammatory diseases.
MicroRNAs are small endogenous noncoding RNAs that are approximately 21 to 22 nucleotides in length which are transcribed from DNA. Finally, the functional miRNAs single strand is loaded into the RNA-induced silencing complex (RISC) to complementary target genes and represses gene expression by destabilizing the target mRNA or by repressing translation.
In this study, after establishing the Treg-of-B cells model, the TaqMan low-density array real-time PCR assay was performed and we found that microRNA-210 was highly expressed in Treg-of-B cells than that of Foxp3+ natural regulatory T cells. To address the expression of microRNA-210 in more detail, we also found that the highest increase in microRNA-210 was observed in Treg-of B cells during induction and different time points activation. Also, the downstream target genes expression of microRNA-210 was lower in Treg-of-B cells compared to that of Foxp3+ natural regulatory T cells. In addition, we also found that microRNA-155 reported to be controlled by Foxp3 and related to regulate Foxp3+ natural regulatory T cells function was also expressed in both Treg-of-B cells and Foxp3+ natural regulatory T cells.
In order to clarify the miRNA function, the miRNA inhibitors transfection into Treg-of-B cells was performed to further investigate the effects of miRNA on Treg-of-B cells. The result showed that the suppressive ability to inhibit responder T cells was decreased after inhibiting microRNA-210 and microRNA-155 expression in Treg-of-B cells, and the cells transfected with microRNA-210 had less suppressive function than microRNA-155 transfected Treg-of-B cells.
Here, we aim to further study the microRNAs profile of Treg-of-B cells and identify significant microRNA that might be engaged in the suppressive function or development of Treg-of-B cells. In this study, we found that the expression of microRNA-210 and microRNA-155 might be the factors involved in the suppressive ability of Treg-of-B cells. Also, the mechanisms and the impacts of these microRNAs are needed to be clarified in detail. With our efforts, we hope to get more information on the function and development of Treg-of-B cells and contribute to Treg-based therapies which might be applied for the treatment of immunological diseases.
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