Emerging roles of noncoding RNAs in T cell differentiation and functions in autoimmune diseases

Roy, Suyasha; Awasthi, Amit

doi:10.1080/08830185.2019.1648454

Cited by 20 publications

(17 citation statements)

References 92 publications

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“…Long non-coding RNAs (lncRNA) are a novel class of functional non-translated RNAs with a length of over 200 nucleotides. Several studies revealed a strong link between lncRNAs and the immune responses [ 59 ]. The expression analysis of lncRNAs in SS patients has shown lncRNAs LINC00657, LINC00511 and CTD-2020K17.1 potentially associated with the disease.…”

Section: Physiopathology Of Sjögren’s Syndromementioning

confidence: 99%

Current State of Knowledge on Primary Sjögren’s Syndrome, an Autoimmune Exocrinopathy

Parisis

Chivasso

Perret

et al. 2020

JCM

106

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Primary Sjögren’s syndrome (pSS) is a chronic systemic autoimmune rheumatic disease characterized by lymphoplasmacytic infiltration of the salivary and lacrimal glands, whereby sicca syndrome and/or systemic manifestations are the clinical hallmarks, associated with a particular autoantibody profile. pSS is the most frequent connective tissue disease after rheumatoid arthritis, affecting 0.3–3% of the population. Women are more prone to develop pSS than men, with a sex ratio of 9:1. Considered in the past as innocent collateral passive victims of autoimmunity, the epithelial cells of the salivary glands are now known to play an active role in the pathogenesis of the disease. The aetiology of the “autoimmune epithelitis” still remains unknown, but certainly involves genetic, environmental and hormonal factors. Later during the disease evolution, the subsequent chronic activation of B cells can lead to the development of systemic manifestations or non-Hodgkin’s lymphoma. The aim of the present comprehensive review is to provide the current state of knowledge on pSS. The review addresses the clinical manifestations and complications of the disease, the diagnostic workup, the pathogenic mechanisms and the therapeutic approaches.

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Section: Physiopathology Of Sjögren’s Syndromementioning

confidence: 99%

Current State of Knowledge on Primary Sjögren’s Syndrome, an Autoimmune Exocrinopathy

Parisis

Chivasso

Perret

et al. 2020

JCM

106

View full text Add to dashboard Cite

show abstract

“…Mounting data have implicated that noncoding RNAs (ncRNAs) primarily including microRNA (miRNA), circular RNA (circRNA), and long ncRNA (lncRNA) play critical roles in mediating inflammation and immune regulation in autoimmune diseases 7 – 9 . Most interestingly, some ncRNAs encapsulated in extracellular vesicles can be found in peripheral circulation and confer modifying effects on joint lesions and tissue regeneration via cell-to-cell communications in rheumatic diseases 10 , 11 .…”

Section: Introductionmentioning

confidence: 99%

CircRNA_09505 aggravates inflammation and joint damage in collagen-induced arthritis mice via miR-6089/AKT1/NF-κB axis

et al. 2020

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A number of circular RNAs (circRNAs) have been implicated in rheumatoid arthritis (RA) pathogenesis; however, little is known about their function and hidden molecular mechanism in immune and inflammation regulation. We investigated the role and the underlying mechanism of circRNA_09505 in RA in this study. Real-time PCR and fluorescence in situ hybridization (FISH) are adopted to estimate the quantitative expression and localization of circRNA_09505 in macrophages. The altering effect of circRNA_09505 on inflammation is investigated in vitro and in vivo by use of macrophage cell models and collagen-induced arthritis (CIA) mice. Luciferase reporter assay and RNA-binding protein immunoprecipitation (RIP) are used to confirm the circRNA_09505/miR-6089 ceRNA network predicted by bioinformatics analysis. Compared with controls, the expression of circRNA_09505 is upregulated in peripheral blood mononuclear cells (PBMCs) from patients with RA. The proliferation and cell cycle are significantly promoted when circRNA_09505 is upregulated in macrophages, whereas knockdown of circRNA_09505 inhibits macrophage proliferation and cell- cycle progression. Besides, circRNA_09505 can act as a miRNA sponge for miR-6089 in macrophages, and promote the production of TNF-α, IL-6, and IL-12 through ceRNA mechanism. Moreover, AKT1 is a direct target of miR-6089. CircRNA_09505 can promote AKT1 expression by acting as a miR-6089 sponge via IκBα/NF-κB signaling pathway in macrophages. Most interestingly, knockdown of circRNA_09505 significantly alleviates arthritis and inflammation in vivo in CIA mice. These data support the hypothesis that circRNA_09505 can function as a miR-6089 sponge and regulate inflammation via miR-6089/AKT1/NF-κB axis in CIA mice.

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“…lncRNAs regulate gene expression independent of protein coding and interact with protein-coding genes in various cell types through multiple processes, such as epigenetic regulation of transcription, mRNA stability, and protein localization [38]. lncRNAs have been shown to be closely related to various immune diseases [39][40][41]. Downregulation of lncRNA ITSN1-2 is associated with rheumatoid arthritis (RA).…”

Section: Discussionmentioning

confidence: 99%

The Role of lncRNA AF117829.1 in the Immunological Pathogenesis of Severe Aplastic Anaemia

Deng

Pan

et al. 2021

Oxidative Medicine and Cellular Longevity

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Objective. Severe aplastic anaemia (SAA) is an autoimmune disease with immune tolerance dysfunction mediated by hyperactivated T lymphocytes that target the haematopoietic system. Numerous studies suggest that long noncoding RNAs (lncRNAs) play a significant role in almost every level of gene function/regulation. However, their specific mechanisms in SAA remain undetermined. This study is aimed at determining the role of key lncRNAs in CD8+ T lymphocytes in the mechanisms of SAA. Methods. RNA-seq was performed to detect all lncRNAs and mRNAs in peripheral CD8+ T lymphocytes from SAA patients and healthy controls. The lncRNA targets were predicted by bioinformatics, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. RT-qPCR was used to verify the expression of key lncRNAs and their predicted targets. We screened lncRNA AF117829.1, which was correlated with autoimmune diseases and downregulated in CD8+ T lymphocytes, and further validated its effects on CD8+ T lymphocytes from SAA patients. Results. We systematically described the lncRNA/mRNA expression changes in CD8+ T lymphocytes in SAA patients and assessed their possible biological functions and signalling pathways. A total of 194 lncRNAs and 2099 mRNAs were changed in SAA patients versus healthy controls. These differentially expressed lncRNAs/mRNAs were associated with organelle components, catalytic activity, the response to stimulation, signal transduction, the immune system and metabolic processes. The downregulated expression of one altered factor, lncRNA AF117829.1, in CD8+ T lymphocytes from SAA patients increased CD8+ T lymphocyte immune function by promoting RIP2 expression. lncRNA AF117829.1 overexpression in CD8+ T lymphocytes reduced perforin and granzyme B expression. The same effect was achieved with GSK583, a RIP2 kinase inhibitor. Conclusions. The proliferation and overactivation of CD8+ T lymphocytes, also known as cytotoxic T cells (CTLs), directly induce bone marrow (BM) failure in SAA patients, but the specific mechanism remains unclear. We found that lncRNA AF117829.1 and its target genes were associated with T cell proliferation, differentiation, and immune dysregulation and that lncRNA AF117829.1 regulated CD8+ T lymphocyte function in SAA patients by promoting RIP2 expression. These findings improve our understanding of the molecular mechanism of immune pathogenesis and provide potential targets for SAA diagnosis and treatment.

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Emerging roles of noncoding RNAs in T cell differentiation and functions in autoimmune diseases

Cited by 20 publications

References 92 publications

Current State of Knowledge on Primary Sjögren’s Syndrome, an Autoimmune Exocrinopathy

Current State of Knowledge on Primary Sjögren’s Syndrome, an Autoimmune Exocrinopathy

CircRNA_09505 aggravates inflammation and joint damage in collagen-induced arthritis mice via miR-6089/AKT1/NF-κB axis

The Role of lncRNA AF117829.1 in the Immunological Pathogenesis of Severe Aplastic Anaemia

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