Excessive expression of miR-27 impairs Treg-mediated immunological tolerance

Cruz, Leilani O.; Hashemifar, Somaye; Wu, Cheng-Jang; Cho, Sunglim; Nguyen, Duc T.; Lin, Ling-Li; Khan, Aly A.; Lu, Li-Fan

doi:10.1172/jci88415

Cited by 48 publications

(36 citation statements)

References 62 publications

(85 reference statements)

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“…1, like mice with T cell-specific overexpression of the miR-23~27~23 cluster (R23CTg), R24Tg mice did not display any abnormality in total thymic or splenic cellularities nor in any peripheral T cell compartment compared to their WT littermates. However, in contrast to the reduced thymic Treg cell frequencies detected in R23CTg mice as well as mice with T cell-specific overexpression of miR-27 (R27Tg) (6, 14), enforced expression of miR-24 in T cells alone resulted in appreciably increased thymic Treg cell numbers (Fig. 1F and G), consistent with the previous notion that miR-24 can antagonize some functions of other members in the miR-23~27~24 family (6).…”

Section: Resultssupporting

confidence: 89%

“…Our recent findings in mice harboring T cells with miR-27 overexpression suggested that the observed autoimmunity was not driven by miR-27 in Tconv cells in a cell-autonomous fashion but rather resulted from a perturbed Treg cell compartment (14). While it is likely miR-24 can directly enhance the production of effector cytokines by Tconv cells, it remains probable that such Tconv cell phenotypes could only be detected in mice lacking a functional Treg cell population as a result of exaggerated miR-24-mediated gene regulation.…”

Section: Resultsmentioning

confidence: 99%

“…Unlike miR-27, the overexpression of which impaired Teff activation and function but promoted disease development through impeding Treg cell-mediated immunoregulation (14), exaggerated miR-24-mediated regulation directly augmented the generation of effector cytokine producing Tconv cells preceding the onset of the autoimmune disorder. It is also noteworthy that R24Tg mice harbored increased thymic Treg cells as opposed to the reduced number observed in R27Tg mice (14). A recent report has suggested a regulatory role of TCF1 in limiting thymic Treg cell development (21).…”

Section: Discussionmentioning

confidence: 99%

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A Novel miR-24–TCF1 Axis in Modulating Effector T Cell Responses

Cho

Nguyen

et al. 2017

The Journal of Immunology

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miR-23~27~24 was recently implicated in restricting Th2 immunity as well as the differentiation and function of other effector T cell lineages. Interestingly, miR-24, unlike other family members, actually promotes Th1 and Th17 responses. Here, we show that miR-24 drives the production of IFNγ and IL-17 in T cells at least in part through targeting TCF1, a transcription factor known for its role in limiting Th1 and Th17 immunity. Surprisingly, while TCF1 was previously shown to promote Th2 responses through inducing GATA3, enforced TCF1 expression in miR-24-overexpresing T cells led to further downregulation of IL-4 and GATA3 expression, suggesting miR-24-mediated inhibition of Th2 immunity cannot be attributed to TCF1 repression by miR-24. Together, our data demonstrates a novel miR-24-TCF1 pathway in controlling effector cytokine production by T cells and further suggests miR-24 could function as a key upstream molecule regulating TCF1-mediated immune responses.

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Section: Resultssupporting

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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A Novel miR-24–TCF1 Axis in Modulating Effector T Cell Responses

Cho

Nguyen

et al. 2017

The Journal of Immunology

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“…24 In addition, excessive expression of miR-27 through preventing Th2 responses and stimulating pathogenic Th1 immunity lead to more inflammation in the body. In contrast, recent studies have reported that IL-10 is directly suppressed by miR-27.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, recent studies have reported that IL-10 is directly suppressed by miR-27. 24 In addition, excessive expression of miR-27 through preventing Th2 responses and stimulating pathogenic Th1 immunity lead to more inflammation in the body. 25 miR-17 has also been identified as negative regulator of suppressive activity of Treg cells by targeting expression of FoxP3 and other transcriptional coregulators, which are involved in determination of Treg cell phenotype.…”

Section: Discussionmentioning

confidence: 99%

The effects of nanocurcumin on Treg cell responses and treatment of ankylosing spondylitis patients: A randomized, double‐blind, placebo‐controlled clinical trial

Ahmadi

Hajialilo

Eghbal‐Fard

et al. 2019

J of Cellular Biochemistry

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Aim Ankylosing spondylitis (AS) is an inflammatory rheumatic disease with increased bone mass in the main sites of inflammation. Regulatory T (Treg) cells have been reported to involve in pathology of AS. This study designed at investigating the effects of nanocurcumin on Treg cell responses in peripheral blood (PB) of AS patients. Methods Test group including 12 AS patients received nanocurcumin daily for 4 months and control group including 12 patients received placebo. The frequency of Treg was measured by flow cytometry. The expression levels of FoxP3 and several associated microRNAs (miRNAs; miR‐27, miR‐17, and miR‐146a) and cytokines including Interleukin‐10 (IL‐10), TGF‐β, and IL‐6 were assessed by real‐time polymerase chain reaction. Furthermore, enzyme‐linked immunosorbent assay was done to determine the secretion levels of cytokines. Results After treatment with nanocurcumin the frequency of Treg cells in AS patients increased significantly. The RT‐PCR data indicated that the expression of miR‐17 and miR‐27 were significantly decreased following nanocurcumin treatment while miR‐146a and FoxP3 were significantly increased. Moreover, nanocurcumin‐treated group had high levels of IL‐10 and TGF‐β and low levels of IL‐6 production than control group. Conclusion The findings suggested that dysregulation of Treg cells in PB influences the AS development and nanocurcumin therapy could regulate the Treg cells, and so could be useful in the treatment of AS and may be other autoimmune diseases. This study is registered with IRCT.ir, number IRCT2017052927520N7.

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The effects of oxygen–ozone therapy on regulatory T‐cell responses in multiple sclerosis patients

Tahmasebi

Qasim²,

Krivenkova

et al. 2021

Cell Biology International

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Multiple sclerosis (MS) is a common degenerative disorder of the central nervous system. The decreased frequency and dysfunction of Treg cells cause inflammation and disease progression. Ozone autohemotherapy can be used as a potential therapeutic approach to regulate the immune system responses and inflammation in MS. For this purpose, 20 relapsing‐remitting multiple sclerosis patients were under treatment with ozone twice weekly for 6 months. The frequency of Treg cell, the expression levels of the Treg cell‐related factors (FoxP3, IL‐10, TGF‐β, miR‐17, miR‐27, and miR‐146A), and the secretion levels of IL‐10 and TGF‐β were assessed. We found a significant increase in the number of Treg cells, expression levels of FoxP3, miRNAs (miR‐17 and miR‐27), IL‐10, and TGF‐β factors in patients after oxygen–ozone (O2‐O3) therapy compared to before treatment. In contrast, oxygen–ozone therapy notably decreased the expression level of miR‐146a in treated patients. Interestingly, the secretion levels of both IL‐10 and TGF‐β cytokines were considerably increased in both serum and supernatant of cultured peripheral blood mononuclear cells in posttreatment condition compared to pretreatment condition. According to results, oxygen–ozone therapy raised the frequency of Treg cell and its relevant factors in treated MS patients. Oxygen–ozone therapy would contribute to improving the MS patients by elevating the Treg cell responses.

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Excessive expression of miR-27 impairs Treg-mediated immunological tolerance

Cited by 48 publications

References 62 publications

A Novel miR-24–TCF1 Axis in Modulating Effector T Cell Responses

A Novel miR-24–TCF1 Axis in Modulating Effector T Cell Responses

The effects of nanocurcumin on Treg cell responses and treatment of ankylosing spondylitis patients: A randomized, double‐blind, placebo‐controlled clinical trial

The effects of oxygen–ozone therapy on regulatory T‐cell responses in multiple sclerosis patients

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