NF-κB-driven miR-34a impairs Treg/Th17 balance via targeting Foxp3

Xie, Mengxiao; Wang, Jingzhe; Gong, W.; Xu, Huiling; Pan, Xiaoyuan; Chen, Yunpeng; Ru, Songwei; Wang, Hui; Chen, Xiaodan; Zhao, Yi; Li, Jing; Yin, Qian; Sheng, Xia; Zhou, Xiaoming; Liu, Xia; Shao, Qixiang

doi:10.1016/j.jaut.2019.04.018

Cited by 81 publications

(73 citation statements)

References 73 publications

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“…They found that the level of murine miR-34a decreases in TGF-β induced Treg cells but increases in Th17 cells induced in vitro. Moreover, the level of miR-34a positively correlates with the Th17 lineage-specific transcription factor RORγt but negatively correlates with the mRNA expression of FOXP3 in PBMCs of SLE, which indicates that miR-34a may play a part in the imbalance of Th17/Treg in SLE (126). In Treg cells of new-onset SLE, the expression of miR-326 is increased and negatively correlates with the mRNA expression of Ets-1 and positively correlates with the levels of CRP and anti-C1q antibodies from new-onset SLE patients, suggesting that miR-326 may regulate Treg cell dysfunction via targeting Est-1 in SLE (127).…”

Section: Ncrnas Regulate the Aberrant Differentiation Of Cd4 + T Subsmentioning

confidence: 98%

Non-Coding RNAs in CD4+ T Cells: New Insights Into the Pathogenesis of Systemic Lupus Erythematosus

et al. 2020

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Non-coding RNAs (ncRNAs) are indispensable for CD4 + T cell differentiation and functions. By directly or indirectly regulating immune gene expression, ncRNAs give flexible instructions to guide the biological processes of CD4 + T cells and play a vital role in maintaining immune homeostasis. However, the dysfunction of ncRNAs alters the gene expression profiles, disturbs the normal biological processes of CD4 + T cells, and leads to the functional changes of CD4 + T cells, which is an underlying cause of systemic lupus erythematosus (SLE). In this review, we focus on the recent advances in the roles of ncRNAs in CD4 + T cell functions and differentiation, as well as their potential applications in the diagnosis and treatment of SLE.

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Section: Ncrnas Regulate the Aberrant Differentiation Of Cd4 + T Subsmentioning

confidence: 98%

Non-Coding RNAs in CD4+ T Cells: New Insights Into the Pathogenesis of Systemic Lupus Erythematosus

et al. 2020

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“…[17] Another study showed that IL-6 enhanced the activity of the promoter of miR-34a by activating the NF-κB/p65 signaling pathway, and further attenuated the expression of forkhead box P3 (Foxp3) by targeting the 3' UTR. [18] Granzyme B was derived from cytotoxic lymphocytes and cytoplasmic granules released by natural killer cells. It mediated apoptosis by activating caspase.…”

Section: Discussionmentioning

confidence: 99%

Genetic Association of rs15672 and rs12640056 Polymorphisms with the Susceptibility of Systemic Lupus Erythematosus in a Chinese Population

Zhang

Zhai

Zhang

et al. 2021

Preprint

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In this study, we aimed to investigate the relationship of IKBKE rs15672 and BANK1 rs12640056 gene polymorphisms with systemic lupus erythematosus (SLE) susceptibility in China. A case-control study was performed on 567 SLE patients and 345 healthy controls. Six single nucleotide polymorphisms (rs15672, rs2296164, rs12640056, rs6842661, rs1957106 and rs2274064) and clinical features were analyzed. Genotyping was executed with improved multiplex ligation detection reaction assay. SNP rs15672 increased the risk (P = 0.028, OR = 1.25, 95%CI = 1.02–1.52) but rs12640056 decreased the risk of SLE (P = 0.015, OR = 0.78, 95%CI = 0.64–0.95). For rs15672, patients carrying allele A assumed high-level IL-6 (25.36 ± 4.64 vs 16.56 ± 2.95, P = 0.036) and IL-4 (12.06 ± 4.51 vs 4.88 ± 1.76, P = 0.047), but low-level granzyme B (14.07 ± 1.86 vs 18.38 ± 3.85, P = 0.023), IL-18 (267.39 ± 14.67 vs 348.57 ± 44.25, P = 0.002) and IL-33 (0.91 ± 0.26 vs 2.19 ± 1.35, P = 0.029). Organ injury showed that mutant genotype at rs15672 had high-prevalence of arthritis (32.02%) and serositis (34.78%), but low in neuropathy (9.09%). For rs12640056, patients carrying allele T assumed low-level IL-33 (0.46 ± 0.17 vs 2.16 ± 1.00, P = 0.009). In conclusion, gene polymorphisms of rs15672 and rs12640056 present relevant with susceptibility of SLE, and affect the expression of cytokine and organ injury.

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“…Although miR-21 levels are negatively correlated with the Th17/Treg ratio in PBMC from RA patients (94), the function of miR-21 in T cells has not been studied. In contrast, miR-34 elevates the Th17/Treg ratio (95,96) and is regulated by GM-CSF and TLR ligands in blood DCs from patients with RA. Moreover, miR-34 drives DC activation and inflammatory cytokine production by targeting AXL, a critical molecular switch that inhibits TLR ligand-induced DC activation (95).…”

Section: Mirnas In Ramentioning

confidence: 93%

“…In CD4 + T cells from RA patients, miR-34a expression is induced by IL-6 and TNF-α through the NF-κB signaling pathway. Furthermore, upregulation of miR-34a disrupts the Th17/Treg balance by targeting FOXP3 and contributes to the progress of collageninduced arthritis in mice (96). Interestingly, IL-6 and TNF-α can also induce miR-10b-5p expression, which dampens IL-17 production by targeting MAP3K7 (97).…”

Section: Mirnas In Ramentioning

confidence: 99%

miRNAs Alter T Helper 17 Cell Fate in the Pathogenesis of Autoimmune Diseases

Huang

Yang

2021

Front. Immunol.

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T helper 17 (Th17) cells are characterized by the secretion of the IL-17 cytokine and are essential for the immune response against bacterial and fungal infections. Despite the beneficial roles of Th17 cells, unrestrained IL-17 production can contribute to immunopathology and inflammatory autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. Although these diverse outcomes are directed by the activation of Th17 cells, the regulation of Th17 cells is incompletely understood. The discovery that microRNAs (miRNAs) are involved in the regulation of Th17 cell differentiation and function has greatly improved our understanding of Th17 cells in immune response and disease. Here, we provide an overview of the biogenesis and function of miRNA and summarize the role of miRNAs in Th17 cell differentiation and function. Finally, we focus on recent advances in miRNA-mediated dysregulation of Th17 cell fate in autoimmune diseases.

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NF-κB-driven miR-34a impairs Treg/Th17 balance via targeting Foxp3

Cited by 81 publications

References 73 publications

Non-Coding RNAs in CD4+ T Cells: New Insights Into the Pathogenesis of Systemic Lupus Erythematosus

Non-Coding RNAs in CD4+ T Cells: New Insights Into the Pathogenesis of Systemic Lupus Erythematosus

Genetic Association of rs15672 and rs12640056 Polymorphisms with the Susceptibility of Systemic Lupus Erythematosus in a Chinese Population

miRNAs Alter T Helper 17 Cell Fate in the Pathogenesis of Autoimmune Diseases

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