The Role of MicroRNAs in Regulatory T Cells

Liu, Chao; Li, Nannan; Liu, Guijian

doi:10.1155/2020/3232061

Cited by 23 publications

(22 citation statements)

References 97 publications

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“…Furthermore, 5 of the identified miRNAs (miR-24-3p/21-5p/125b/5p/29a-3p/27a-3p) were described to reduce IFNγ expression, while only miR-19b-3p was able to promote its upregulation. Second, focusing the search on miRNAs was reported to have a specific influence on T reg activation/proliferation [ 45 ]: 2 resulted in inducing, 4 in blocking and 1 had an ambiguous role ( Table 2 ). Intriguingly, overall, promoting miRNAs far exceeded by 2.84 fold those players reducing T reg expansion and activation.…”

Section: Resultsmentioning

confidence: 99%

Cartilage Protective and Immunomodulatory Features of Osteoarthritis Synovial Fluid-Treated Adipose-Derived Mesenchymal Stem Cells Secreted Factors and Extracellular Vesicles-Embedded miRNAs

Ragni

Colombini

Viganò

et al. 2021

Cells

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Intra-articular administration of adipose-derived mesenchymal stem cells (ASCs), either in vitro expanded or within adipose tissue-based products obtained at point-of-care, has gained popularity as innovative regenerative medicine approach for osteoarthritis (OA) treatment. ASCs can stimulate tissue repair and immunomodulation through paracrine factors, both soluble and extracellular vesicles (EV) embedded, collectively defining the secretome. Interaction with the degenerative/inflamed environment is a crucial factor in understanding the finely tuned molecular message but, to date, the majority of reports have described ASC-secretome features in resting conditions or under chemical stimuli far from the in vivo environment of degenerated OA joints. In this report, the secretory profile of ASCs treated with native synovial fluid from OA patients was evaluated, sifting 200 soluble factors and 754 EV-embedded miRNAs. Fifty-eight factors and 223 EV-miRNAs were identified, and discussed in the frame of cartilage and immune cell homeostasis. Bioinformatics gave a molecular basis for M2 macrophage polarization, T cell proliferation inhibition and T reg expansion enhancement, as well as cartilage protection, further confirmed in an in vitro model of OA chondrocytes. Moreover, a strong influence on immune cell chemotaxis emerged. In conclusion, obtained molecular data support the regenerative and immunomodulatory properties of ASCs when interacting with osteoarthritic joint environment.

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Section: Resultsmentioning

confidence: 99%

Cartilage Protective and Immunomodulatory Features of Osteoarthritis Synovial Fluid-Treated Adipose-Derived Mesenchymal Stem Cells Secreted Factors and Extracellular Vesicles-Embedded miRNAs

Ragni

Colombini

Viganò

et al. 2021

Cells

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“…miR-146a regulates IL-1b expression (48)(49)(50), and IL-1b plays an important role in tumor progression by enhancing angiogenesis, amplifying myeloid-derived suppressive cells (MDSCs) and shifting macrophages towards an M2 phenotype (51,52). miR-146a and miR-155 are expressed in Treg cells (53), and there was a negative correlation between miR-146a and the frequency of Treg cells in NSCLC patients with a GG genotype. Furthermore, there was a positive correlation between miR-155 and CTLA4+ T-cell frequency in patients with an AT genotype.…”

Section: Discussionmentioning

confidence: 99%

Evaluation Expression of miR-146a and miR-155 in Non-Small-Cell Lung Cancer Patients

et al. 2021

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BackgroundNon−small-cell lung cancer (NSCLC) is the major type of lung cancer. MicroRNAs (miRNAs) are novel markers and targets in cancer therapy and can act as both tumor suppressors and oncogenes and affect immune function. The aim of this study was to investigate the expression of miR146a and miR155 in linked to blood immune cell phenotypes and serum cytokines in NSCLC patients.MethodsThirty-three NSCLC patients and 30 healthy subjects were enrolled in this study. The allele frequencies of potential DNA polymorphisms were studied using polymerase chain reaction (PCR)–restriction fragment length polymorphism (PCR-RFLP) analysis in peripheral blood samples. Quantitative reverse transcription PCR (qRT-PCR) was used to measure the expression of miR-146a and miR-155 in peripheral blood mononuclear cells (PBMCs). Serum cytokine (IL-1β, IL-6, TNF-α, TGF-β, IL-4, IFN-γ) levels were determined by ELISA. The frequency of circulating CD3+CTLA-4+ and CD4+CD25+FOXP3+ (T regulatory cells/Treg) expression was measured by flow cytometry.ResultsmiR-146a was significantly downregulated in PBMC of NSCLC patients (P ≤ 0.001). Moreover, IL-6 and TGF-β levels were elevated in NSCLC patients (P ≤ 0.001, P ≤ 0.018, respectively). CD3+ CTLA-4+ and Treg cells frequencies were higher in patients than in control subjects (P ≤ 0.0001, P ≤ 0.0001, respectively). There was a positive correlation between miR-155 and IL-1β levels (r=0.567, p ≤ 0.001) and a negative correlation between miR-146a and TGF-β levels (r=-0.376, P ≤ 0.031) in NSCLC patients. No significant differences were found in the relative expression of miR-146a and miR-155, cytokine levels or immune cell numbers according to miR-146a and miR-155 (GG/GC/CC, TT/AT/AA) genotypes. However, there was a positive correlation between miR-146a and IL-1β levels (r=0.74, P ≤ 0.009) in GG subjects and a positive correlation between miR-146a expression and CD3+CTLA4+ cell frequency (r=0.79, P ≤ 0.01) in CC genotyped subjects. Conversely, a negative correlation between miR-146a expression and Treg cell frequency (r=−0.87, P ≤ 0.05) was observed with the GG genotype. A positive correlation between miR-155 and IL-1β expression (r=0.58, p ≤ 0.009) in the TT genotype and between miR-155 expression and CD3+CTLA-4 cell frequency (r=0.75, P ≤ 0.01) was observed in the AT genotype.ConclusionsThe current data suggest that the miR-146a expression in PBMC and serum TGF-β and IL-1β levels may act as blood markers in NSCLC patients. Further study is needed to elucidate the link between immune cells and serum miR146 at early disease stages.

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“…The role of microRNAs in immune cell lineage differentiation and their physiological functions in maintaining normal innate and adaptive responses is well known [50,51]. Aberrations in the miRNA-mediated immune-cell development and function regulation have been related to autoimmune diseases [52][53][54]. Intuitively, miRNA dysregulation is one of the main contributors to the collapse of selftolerance, leading to autoimmunity [55].…”

Section: Discussionmentioning

confidence: 99%

Regulation of CD4+CD25+FOXP3+ Treg Cells in Systemic Lupus Erythematosus (SLE): Association With miRNAs Expression

El-maadawy

et al. 2021

Preprint

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Various genetic factors are controlling regulatory cells T (Treg) cell function, such as miRNAs. Interfering in the miRNA synthesis pathway in Treg cells could result in loss of Tregs' regulatory function, leading to the promotion of inflammatory settings and autoimmunity. This study was designed to investigate the role of miRNA in regulating Treg cells in SLE patients. Treg's frequency was determined using flow cytometry in 100 SLE patients’ and100 healthy controls. Expression of miR-21, miR-24, miR125, miR-146a, miR-148a, and miR-155 was estimated in peripheral blood mononuclear cells (PBMCs) using quantitative real-time polymerase chain reaction (qRT-PCR). The ROC curve evaluated the diagnostic role of miRNAs in SLE. A significant elevation (p<0.001) in Treg cells in SLE patients than controls was observed, with a maximum increase inactive SLE cases. SLE patients exhibit a significant increase in miR-21 (p<0.01), miR-148a (p<0.001), miR-146a (p<0.05) and miR-155 (p<0.001) and significant reduction in miR-24 (p<0.001). An insignificant decrease in miR-125 was observed in SLE patients. The best sensitivity and specificity were detected in miR-148a (88%, 70%) at a cutoff value of 1. 065. Tregs were positively correlated with miR-21(r=0.333, p<0.05), miR-146a (r=0.589, p<0.01) and miR-148a (r=0.309, p<0.05). In conclusion, this research provides a piece of novel information regarding Treg cells' in SLE patients. Our results pointed to the substantial role of miRNAs in controlling Treg cells in lupus. To validate our interesting results, more researches are needed.

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The Role of MicroRNAs in Regulatory T Cells

Cited by 23 publications

References 97 publications

Cartilage Protective and Immunomodulatory Features of Osteoarthritis Synovial Fluid-Treated Adipose-Derived Mesenchymal Stem Cells Secreted Factors and Extracellular Vesicles-Embedded miRNAs

Cartilage Protective and Immunomodulatory Features of Osteoarthritis Synovial Fluid-Treated Adipose-Derived Mesenchymal Stem Cells Secreted Factors and Extracellular Vesicles-Embedded miRNAs

Evaluation Expression of miR-146a and miR-155 in Non-Small-Cell Lung Cancer Patients

Regulation of CD4+CD25+FOXP3+ Treg Cells in Systemic Lupus Erythematosus (SLE): Association With miRNAs Expression

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