miR-17∼92 family clusters control iNKT cell ontogenesis via modulation of TGF-β signaling

Fedeli, Maya; Riba, Michela; Manteiga, Jose Manuel Garcia; Tian, Lei; Viganò, Valentina; Rossetti, Grazisa; Pagani, Massimiliano; Xiao, Changchun; Liston, Adrian; Stupka, Elia; Cittaro, Davide; Abrignani, Sergio; Provero, Paolo; Dellabona, Paolo

doi:10.1073/pnas.1612024114

Cited by 42 publications

(37 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some miRNAs also play important roles in regulating immune function and maintaining immune homeostasis, such as miR-223-3p and miR-155-5p (120–122). It is not surprising that abnormal expressions of miRNAs involving immune function can potentially contribute to the development of autoimmune diseases (123, 124). Recent studies have revealed that some miRNAs are also involved in the development of AITD, and most of them have been found to be intensively involved in modulating the differentiation or activation of immune cells and immune response (Table 1).…”

Section: Epigenetics In Aitdmentioning

confidence: 99%

The Emerging Role of Epigenetics in Autoimmune Thyroid Diseases

et al. 2017

View full text Add to dashboard Cite

Autoimmune thyroid diseases (AITD) are a group of both B cell- and T cell-mediated organ-specific autoimmune diseases. Graves’ disease and Hashimoto thyroiditis are the two main clinical presentations of AITD. Both genetic and environmental factors have important roles in the development of AITD. Epigenetics have been considered to exert key roles in integrating those genetic and environmental factors, and epigenetic modifications caused by environmental factors may drive genetically susceptibility individuals to develop AITD. Recent studies on the epigenetics of AITD have provided some novel insights into the pathogenesis of AITD. The aim of this review is to provide an overview of recent advances in the epigenetic mechanisms of AITD, such as DNA methylation, histone modifications, and non-coding RNAs. This review highlights the key roles of epigenetics in the pathogenesis of AITD and potential clinical utility. However, the epigenetic roles in AITD are still not fully elucidated, and more researches are needed to provide further deeper insights into the roles of epigenetics in AITD and to uncover new therapeutic targets. Although there are many studies assessing the epigenetic modifications in AITD patients, the clinical utility of epigenetics in AITD remains poorly defined. More studies are needed to identify the underlying epigenetic modifications that can contribute to accurate diagnosis of AITD, adequate choice of treatment approach, and precise prediction of treatment outcomes.

show abstract

Section: Epigenetics In Aitdmentioning

confidence: 99%

The Emerging Role of Epigenetics in Autoimmune Thyroid Diseases

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Mir‐150 is required for iNKT cell maturation and its loss results in increased interferon‐ γ (IFN‐ γ ) production, miR‐181 is essential for the early development of iNKT cells and Let‐7 miRNAs specifically target Promyelocytic leukemia zinc finger protein (PLZF) expression during iNKT cell development in the thymus . Recently, it was shown that the miRNA cluster miR17~92 regulates iNKT cell development through regulation of transforming growth factor‐ β …”

Section: Introductionmentioning

confidence: 99%

Invariant natural killer T‐cell development and function with loss of microRNA‐155

et al. 2017

View full text Add to dashboard Cite

Invariant natural killer T (iNKT) cells are adaptive T cells with innate-like characteristics including rapid cytokine production and a proliferative response to stimulation. Development of these cells in the thymus is dependent on expression of the microRNA (miRNA) processing enzyme Dicer, indicating that iNKT cells probably have distinct miRNA requirements for gene regulation during development. The miRNA miR-155 has previously been shown to have numerous roles in T cells, including regulation of proliferation and differentiation, and positive modulation of interferon-γ expression. We examined the role of miR-155 in the development and function of iNKT cells. Using germline-deficient miR-155 mice, we showed that loss of miR-155 resulted in unchanged iNKT cell frequency and cell number. Although miR-155 was up-regulated in iNKT cells upon activation with α-galactosylceramide, loss of miR-155 did not affect cytokine production or proliferation by iNKT cells. Hence, cytokine production occurs in iNKT cells independently of miR-155 expression.

show abstract

“…miRNAs are short noncoding RNAs with a length of 18-22 nucleotides that cause mRNA cleavage and subsequent degradation by binding to the complementary 3′-UTR of the mRNA. miR-17 has been shown to control iNKT cell oncogenes is via modulation of TGF-β signaling [24], and TGF-β signaling plays an important role in Treg differentiation [25]. Therefore, we evaluated the effect of miR-17 on TGFBR II expressed by T cells and found that the expression of TGFBR II on the cultured CD4 + T cells was significantly decreased after transfecting with miR-17, and siTGFBR II resulted in a similar reduction in the frequency of Tregs, suggesting that miR-17 regulated the Treg differentiation by inhibiting TGFBR II expression.…”

Section: Discussionmentioning

confidence: 99%

Circulating Exosomal miR-17 Inhibits the Induction of Regulatory T Cells via Suppressing TGFBR II Expression in Rheumatoid Arthritis

Wang

Jia

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: A reduced prevalence of circulating regulatory T cells (Tregs)is a hallmark of inflammatory rheumatoid arthritis (RA). However, the underlying mechanisms of alterations of Tregs are unclear. Methods: The ratio of Tregs in peripheral blood of healthy controls (HCs) and patients with RA was determined by flow cytometry. MicroRNA (miRNA) expression profiles in exosomes derived from RA patients (RA-exosomes) and in those from HCs (HC-exosomes) were detected by microarray analysis, and miR-17 was measured by quantitative real-time PCR. Transforming growth factor beta receptor II (TGFBR II) expressed by T cells was measured by flow cytometry. The interaction between miR-17 and TGFBR II was evaluated by dual-luciferase reporter assay. Results: We found that RA-exosomes can selectively affect Treg differentiation in vitro. Several miRNAs are more abundant in the RA-exosomes than in HC-exosomes. Among those upregulated in patients with RA, miR-17 can suppress Treg induction by inhibiting the expression of TGFBR II. Conclusion: Our findings imply that altered miRNA expression in RA-exosomes may contribute to the pathogenesis of RA by disrupting the homeostasis of Tregs.

show abstract

miR-17∼92 family clusters control iNKT cell ontogenesis via modulation of TGF-β signaling

Cited by 42 publications

References 50 publications

The Emerging Role of Epigenetics in Autoimmune Thyroid Diseases

The Emerging Role of Epigenetics in Autoimmune Thyroid Diseases

Invariant natural killer T‐cell development and function with loss of microRNA‐155

Circulating Exosomal miR-17 Inhibits the Induction of Regulatory T Cells via Suppressing TGFBR II Expression in Rheumatoid Arthritis

Contact Info

Product

Resources

About