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Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
Published on: June 15, 2016
The aberrant expression of microRNAs and correlations with T cell subsets in patients with immune thrombocytopenia
Lu Liu1, Mingqiang Hua1, Chuanfang Liu1
1Department of Hematology, Qilu Hospital, Shandong University, Jinan, China.
Abstract:
Both microRNAs and T helper (Th) cells involve in autoimmune diseases and their effects and interactions in immune thrombocytopenia (ITP) remain unclear. In the present study, we investigated the expression profiles of seven immune-related microRNAs (miR-155, 146a, 326, 142-3p, 17-5p, 21 and 181a) and the frequencies of four Th cells (Th1, Th2, Th17 and Treg) in peripheral blood mononuclear cell (PBMCs) of ITP patients and healthy controls. Platelet autoantibodies specific for GPIIb/IIIa or GPIb/IX were measured using MAIPA method. The regulating effect of miR-146a on Th differentiation was evaluated after using agomir. Our results showed that the expression of miR-146a, miR-326 or miR-142-3p in ITP patients was lower than that of controls. The frequencies of Treg cells were decreased, whereas the frequencies of Th17 and Th22 cells were increased significantly in ITP patients compared to those in controls. The expression levels of miR-142-3p and miR-146a were negatively correlated with Th17 cells,respectively. The expression of miR-146a was positively correlated with the frequencies of Treg cells and platelet counts.No significant correlation was found between the miRNAs expression and different autoantibody groups. The up-regulated miR-146a expression with agomir contributed to the differentiation of Th17 and Treg in ITP patients.Moreover, miR-146a was increased in the presence of DEX in PBMCs of ITP patients in vitro.Our study represents the abnormal expression profile of immune-related miRNAs in ITP patients, and miR-146a may be involved in Tregs differentiation and function.
Insights
Immune thrombocytopenia (ITP) involves altered microRNA and T helper cell levels. MiR-146a may regulate T regulatory cells and influence ITP, showing potential as a therapeutic target.
Area of Science:
- Immunology
- Molecular Biology
- Hematology
Background:
- Autoimmune diseases like immune thrombocytopenia (ITP) involve complex immune dysregulation.
- The roles of microRNAs (miRNAs) and T helper (Th) cells in ITP pathogenesis are not fully understood.
Purpose of the Study:
- To investigate immune-related miRNA expression profiles and Th cell frequencies in ITP patients.
- To explore the regulatory effect of miR-146a on Th cell differentiation in ITP.
Main Methods:
- Quantification of seven immune-related miRNAs and four Th cell subsets (Th1, Th2, Th17, Treg) in peripheral blood mononuclear cells (PBMCs) from ITP patients and healthy controls.
- Measurement of platelet autoantibodies using the MAIPA assay.
- In vitro evaluation of miR-146a's effect on Th differentiation using agomir and dexamethasone (DEX).
Main Results:
- Lower expression of miR-146a, miR-326, and miR-142-3p observed in ITP patients compared to controls.
- Increased frequencies of Th17 and Th22 cells, with decreased Treg cells, in ITP patients.
- Negative correlation between miR-142-3p/miR-146a and Th17 cells; positive correlation between miR-146a and Treg cells/platelet counts.
- Upregulated miR-146a promoted Th17 and Treg differentiation and was induced by DEX in ITP PBMCs.
Conclusions:
- ITP is characterized by distinct immune-related miRNA expression profiles and altered Th cell populations.
- miR-146a plays a significant role in regulating Treg differentiation and function in ITP.
- miR-146a modulation presents a potential therapeutic strategy for ITP.
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