MicroRNA-181c promotes Th17 cell differentiation and mediates experimental autoimmune encephalomyelitis

Zhang, Zimu; Xue, Zhenyi; Liu, Ying; Liu, Hongkun; Guo, X. Edward; Li, Yan; Yang, Hongwei; Zhang, Lijuan; Da, Yurong; Yao, Zhi; Zhang, Rongxin

doi:10.1016/j.bbi.2018.03.011

Cited by 53 publications

(47 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Unfortunately, the effect of the decrease of SMAD7 gene expression on SMAD2/SMAD3 phosphorylation could not be studied in our patients because no protein extract was collected from CD4+T cells. In agreement with the lower SMAD7 levels in CD4+ T cells from the peripheral blood of MS patients observed in the present work, Zhang et al found values for the microRNA miR-181, a SMAD7 inhibitor, to be increased in the same cells of MS patients, thus suggesting an increase in TGF-β-mediated Th17 differentiation [32]. In the same way, Meoli et al showed that SMAD7 was downregulated in the CD4+ T lymphocytes of RRMS patients and that TGF-β regulates overexpression of SMAD7 [33].…”

Section: Discussionsupporting

confidence: 92%

Differential Expression of SMAD Genes and S1PR1 on Circulating CD4+ T Cells in Multiple Sclerosis and Crohn’s Disease

Abarca-Zabalía

García

Ros

et al. 2020

IJMS

View full text Add to dashboard Cite

The Th17 immune response plays a key role in autoimmune diseases such as multiple sclerosis (MS) and inflammatory bowel disease (IBD). Expression of Th17-related genes in inflamed tissues has been reported in autoimmune diseases. However, values are frequently obtained using invasive methods. We aimed to identify biomarkers of MS in an accessible sample, such as blood, by quantifying the relative expression of 91 Th17-related genes in CD4+ T lymphocytes from patients with MS during a relapse or during a remitting phase. We also compared our findings with those of healthy controls. After confirmation in a validation cohort, expression of SMAD7 and S1PR1 mRNAs was decreased in remitting disease (–2.3-fold and –1.3-fold, respectively) and relapsing disease (–2.2-fold and –1.3-fold, respectively). No differential expression was observed for other SMAD7-related genes, namely, SMAD2, SMAD3, and SMAD4. Under-regulation of SMAD7 and S1PR1 was also observed in another autoimmune disease, Crohn’s disease (CD) (−4.6-fold, -1.6-fold, respectively), suggesting the presence of common markers for autoimmune diseases. In addition, expression of TNF, SMAD2, SMAD3, and SMAD4 were also decreased in CD (–2.2-fold, –1.4-fold, –1.6-fold, and –1.6-fold, respectively). Our study suggests that expression of SMAD7 and S1PR1 mRNA in blood samples are markers for MS and CD, and TNF, SMAD2, SMAD3, and SMAD4 for CD. These genes could prove useful as markers of autoimmune diseases, thus obviating the need for invasive methods.

show abstract

Section: Discussionsupporting

confidence: 92%

Differential Expression of SMAD Genes and S1PR1 on Circulating CD4+ T Cells in Multiple Sclerosis and Crohn’s Disease

Abarca-Zabalía

García

Ros

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Interleukin-21 and IL-6 are two cytokines that can positively regulate Th17 differentiation. 31,59 Overexpression of miR-21 reduced SMAD-7 expression while upregulating SMAD-2/3 levels, resulting in enhanced IL-17 production. 23,26 Because IL-6 is also a strong suppressor of the TGF-b-driven induction of Foxp3, 57 miR-26a could also promote the development and function of Treg cells.…”

Section: Targets Of Dysregulated Mirnas In T Cellsmentioning

confidence: 99%

“…miR-21 and miR-181c could promote Th17 cell differentiation through direct targeting of SMAD-7. 31,59 Overexpression of miR-21 reduced SMAD-7 expression while upregulating SMAD-2/3 levels, resulting in enhanced IL-17 production. However, Treg cell differentiation was normal in miR-21-deficient mice.…”

Section: Targets Of Dysregulated Mirnas In T Cellsmentioning

confidence: 99%

MicroRNA‐mediated regulation of T helper type 17/regulatory T‐cell balance in autoimmune disease

et al. 2018

View full text Add to dashboard Cite

T helper type 17 (Th17) cells and regulatory T (Treg) cells are two distinct T-cell subsets with opposite effects on immune functions. While Th17 cells are a key effector in the immune response and play critical roles in the development of autoimmunity and inflammation, Treg cells orchestrate the overall immune response and maintain peripheral immune tolerance by regulating the activity of the effector T cells. However, the developmental pathways for Th17 and Treg cells are reciprocally interconnected and there is a significant amount of plasticity between them. Disturbed Th17/Treg balance contributes to the development of autoimmune diseases, like experimental autoimmune encephalomyelitis and multiple sclerosis. MicroRNAs (miRNAs) are small non-coding RNA molecules that post-transcriptionally regulate gene expression. Recently, emerging evidence demonstrates that miRNAs play an important role in regulating the pathogenesis of autoimmune diseases through the modulation of Th17/Treg balance. This review will provide an overview of the dysregulated miRNAs and their functions in modulating the Th17/Treg balance in autoimmune diseases.

show abstract

“…Th17 development is regulated by miRNAs, such as miR‐326, which targets the TF Ets‐1, a negative regulator on Th17 differentiation . Th17 cell differentiation is also regulated by miR‐181c, which targets Smad7, a negative regulator of TGF‐β signaling, resulting in increased TGF‐β‐induced Smad2/3 signaling followed by inhibition of IL‐2 functions (Th17 cell differentiation inhibitor) …”

Section: Immune Cell Pathways Regulated By Mirnas In Cancermentioning

confidence: 99%

Role of miRNAs in immune responses and immunotherapy in cancer

Cortez

Anfossi

Ramapriyan

et al. 2019

Genes Chromosomes & Cancer

112

View full text Add to dashboard Cite

In the past decade, the study of mechanisms of cancer immunity has seen a prominent boom, which paralleled the increased amount of research on the clinical efficacy of immune checkpoint blockade in several lethal types of cancers. This conspicuous effort has led to the development of successful immunotherapy treatment strategies, whose medical impact has been recognized by the awarding of 2018 Nobel Prize in Physiology or Medicine to the two pioneers of check point inhibitor research, Tasuku Honjo and James Allison. Despite these promising achievements, the differences in the clinical response rate in different cancer patients and the high risk of toxicity of immune‐based therapies represent crucial challenges. More remarkably, the causes responsible for different outcome (success vs failure) in patients with tumor having same histotype and clinical characteristics remain mostly unknown. MicroRNAs (miRNAs), small regulatory noncoding RNA molecules representing the most studied component of the dark matter of the human genome, are involved in the regulation of many pathways of cancer and immune cells. Therefore, understanding the role of miRNAs in controlling cancer immunity is necessary, as it can contribute to reveal mechanisms that can be modulated to improve the success of immunetherapy in cancer patients. Here, we discuss the latest findings on immune pathways regulated by miRNAs in cancer, miRNA‐mediated regulation of immune cells in the tumor microenvironment, and miRNAs as potential target for immunotherapies.

show abstract

MicroRNA-181c promotes Th17 cell differentiation and mediates experimental autoimmune encephalomyelitis

Cited by 53 publications

References 41 publications

Differential Expression of SMAD Genes and S1PR1 on Circulating CD4+ T Cells in Multiple Sclerosis and Crohn’s Disease

Differential Expression of SMAD Genes and S1PR1 on Circulating CD4+ T Cells in Multiple Sclerosis and Crohn’s Disease

MicroRNA‐mediated regulation of T helper type 17/regulatory T‐cell balance in autoimmune disease

Role of miRNAs in immune responses and immunotherapy in cancer

Contact Info

Product

Resources

About