Increased expression of long noncoding RNAs LOC100652951 and LOC100506036 in T cells from patients with rheumatoid arthritis facilitates the inflammatory responses

Abstract Background Dinotefuran (CAS No. 165252–70-0), a neonicotinoid insecticide, has been used to protect various crops against invertebrate pests and has been associated with numerous negative sublethal effects on honey bees. Long noncoding RNAs (lncRNAs) play important roles in mediating various biological and pathological processes, involving transcriptional and gene regulation. The effects of dinotefuran on lncRNA expression and lncRNA function in the honey bee brain are still obscure. Results Through RNA sequencing, a comprehensive analysis of lncRNAs and mRNAs was performed following exposure to 0.01 mg/L dinotefuran for 1, 5, and 10 d. In total, 312 lncRNAs and 1341 mRNAs, 347 lncRNAs and 1458 mRNAs, and 345 lncRNAs and 1155 mRNAs were found to be differentially expressed (DE) on days 1, 5 and 10, respectively. Gene set enrichment analysis (GSEA) indicated that the dinotefuran-treated group showed enrichment in carbohydrate and protein metabolism and immune-inflammatory responses such as glycine, serine and threonine metabolism, pentose and glucuronate interconversion, and Hippo and transforming growth factor-β (TGF-β) signaling pathways. Moreover, the DE lncRNA TCONS_00086519 was shown by fluorescence in situ hybridization (FISH) to be distributed mainly in the cytoplasm, suggesting that it may serve as a competing endogenous RNA and a regulatory factor in the immune response to dinotefuran. Conclusion This study characterized the expression profile of lncRNAs upon exposure to neonicotinoid insecticides in young adult honey bees and provided a framework for further study of the role of lncRNAs in honey bee growth and the immune response.

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Long noncoding RNAs expression profile and functional networks in rheumatoid arthritis

Oncotarget ◽

10.18632/oncotarget.20036 ◽

2017 ◽

Vol 8 (56) ◽

pp. 95280-95292 ◽

Cited By ~ 7

Author(s):

Donghua Xu ◽

Ye Jiang ◽

Lu Yang ◽

Xixing Hou ◽

Jihong Wang ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Expression Profile ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Functional Networks

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THU0078 EXPRESSION PROFILE ANALYSIS OF LONG NONCODING RNAS INDUCED BY IL-1ß IN RHEUMATOID ARTHRITIS FIBROBLAST-LIKE SYNOVIOCYTES

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3072 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 251.1-251

Author(s):

J. M. Kim ◽

H. J. Kang ◽

S. J. Jung ◽

B. W. Song ◽

H. J. Jeong ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Expression Profile ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Aberrant Expression ◽

Iκb Kinase ◽

Ngs Data ◽

Fibroblast Like Synoviocytes

Background:Long noncoding RNAs (lncRNAs) have recently emerged as important biological regulators and the aberrant expression of lncRNAs has been reported in various diseases including cancer, cardiovascular disease, and diabetes mellitus. However, the role of lncRNAs in the pathogenesis of rheumatoid arthritis (RA) remains unknown.Objectives:Thus, we studied lncRNAs influenced by IL-1, which is one of the key mediators in the pathogenesis of RA, and also investigated whether regulation of NF-κB activation, which is known to be induced by IL-1, could lead to the changes of expression of those lncRNAs.Methods:Fibroblast-like synoviocytes (FLS) were obtained from the knee joints of the patients with RA. The next-generation sequencing (NGS) data were analyzed to identify differentially expressed lncRNAs between unstimulated RA FLS and IL-1-stimulated RA FLS. The expression levels of the top 5 candidates in NGS data were validated by RT-qPCR using extended number of unstimulated RA FLS and IL-1-stimulated RA FLS. IMD-0560, an inhibitor of IκB kinase (IKK) was used for the regulation of NF-κB activation. Activation and inhibition of NF-κB were confirmed by Western blotting. Changed expressions of the lncRNAs were identified by RT-qPCR.Results:NGS analysis revealed up-regulated 30 lncRNAs and down-regulated 15 lncRNAs in IL-1-treated RA FLS compared with unstimulated RA FLS. Top 5 lncRNAs were selected among 30 lncRNAs up-regulated by IL-1 in RA FLS based on fold-change with P-value cutoff. The up-regulated lncRNAs including NR_046035, NR_027783, NR_033422, NR_003133, and NR_049759 were validated by RT-qPCR. IMD-0560 inhibited phosphorylation of IκBα induced by IL-1 in RA FLS. Overexpression of lncRNAs induced by IL-1 was also inhibited by IMD-0560 in RA FLS.Conclusion:Our study revealed that IL-1 increased the expression of NR_046035, NR_027783, NR_033422, NR_003133, and NR_049759 in RA FLS. In addition, the expression of these lncRNAs was regulated by inhibition of NF-κB activation. Thus, our data suggest that the lncRNAs might be involved in the pathogenesis of RA through NF-κB signaling pathway.References:[1]Long noncoding RNAs and human disease. Trends Cell Biol. 2011 Jun;21(6):354-61.[2]A long noncoding RNA mediates both activation and repression of immune response genes. Science. 2013 Aug 16;341(6147):789-92.[3]Long noncoding RNA expression profile in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Arthritis Res Ther. 2016 Oct 6;18(1):227.Disclosure of Interests:None declared

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Egr2 and 3 control inflammation, but maintain homeostasis, of PD-1high memory phenotype CD4 T cells

Life Science Alliance ◽

10.26508/lsa.202000766 ◽

2020 ◽

Vol 3 (9) ◽

pp. e202000766

Author(s):

Alistair LJ Symonds ◽

Wei Zheng ◽

Tizong Miao ◽

Haiyu Wang ◽

TieShang Wang ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

T Cells ◽

Cd4 T Cells ◽

Active Rheumatoid Arthritis ◽

Inflammatory Responses ◽

Homeostatic Proliferation ◽

Adaptive Responses ◽

Memory Phenotype ◽

Adaptive Immune ◽

Cd4 Cell

The transcription factors Egr2 and 3 are essential for controlling inflammatory autoimmune responses of memory phenotype (MP) CD4 T cells. However, the mechanism is still unclear. We have now found that the Egr2+ subset (PD-1high MP) of MP CD4 T cells expresses high levels of checkpoint molecules (PD-1 and Lag3) and also markers of effector T cells (CXCR3 and ICAM-1). Egr2/3 are not required for PD-1high MP CD4 cell development but mediate a unique transcriptional programme that effectively controls their inflammatory responses, while promoting homeostatic proliferation and adaptive responses. Egr2 negative PD-1high MP CD4 T cells are impaired in homeostatic proliferation and adaptive responses against viral infection but display inflammatory responses to innate stimulation such as IL-12. PD-1high MP CD4 T cells have recently been implicated in rheumatoid arthritis pathogenesis, and we have now found that Egr2 expression is reduced in PD-1high MP CD4 T cells from patients with active rheumatoid arthritis compared with healthy controls. These findings demonstrate that Egr2/3 control the inflammatory responses of PD-1high MP CD4 T cells and maintain their adaptive immune fitness.

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Expression of novel long noncoding RNAs defines virus-specific effector and memory CD8+ T cells

Nature Communications ◽

10.1038/s41467-018-07956-7 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 14

Author(s):

William H. Hudson ◽

Nataliya Prokhnevska ◽

Julia Gensheimer ◽

Rama Akondy ◽

Donald J. McGuire ◽

...

Keyword(s):

T Cells ◽

Cd8 T Cells ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Memory Cd8 T Cells ◽

Specific Effector

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Profiles of Long Noncoding RNAs in Human Naive and Memory T Cells

The Journal of Immunology ◽

10.4049/jimmunol.1700232 ◽

2017 ◽

Vol 199 (2) ◽

pp. 547-558 ◽

Cited By ~ 18

Author(s):

Charles F. Spurlock ◽

Guzel Shaginurova ◽

John T. Tossberg ◽

Jonathan D. Hester ◽

Nathaniel Chapman ◽

...

Keyword(s):

T Cells ◽

Memory T Cells ◽

Noncoding Rnas ◽

Long Noncoding Rnas

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Human adipose-derived mesenchymal stem cells reduce inflammatory and T cell responses and induce regulatory T cells in vitro in rheumatoid arthritis

Annals of the Rheumatic Diseases ◽

10.1136/ard.2008.101881 ◽

2009 ◽

Vol 69 (01) ◽

pp. 241-248 ◽

Cited By ~ 244

Author(s):

E Gonzalez-Rey ◽

M A Gonzalez ◽

N Varela ◽

F O’Valle ◽

P Hernandez-Cortes ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Stem Cells ◽

T Cells ◽

Mesenchymal Stem Cells ◽

T Cell ◽

Regulatory T Cells ◽

Inflammatory Responses ◽

T Cell Responses ◽

Cell Responses ◽

Adult Mesenchymal Stem Cells

Objectives:Adult mesenchymal stem cells were recently found to suppress effector T cell and inflammatory responses and have emerged as attractive therapeutic candidates for immune disorders. In rheumatoid arthritis (RA), a loss in the immunological self-tolerance causes the activation of autoreactive T cells against joint components and subsequent chronic inflammation. The aim of this study is to characterise the immunosuppressive activity of human adipose-derived mesenchymal stem cells (hASCs) on collagen-reactive T cells from patients with RA.Methods:The effects of hASCs on collagen-reactive RA human T cell proliferation and cytokine production were investigated, as well as effects on the production of inflammatory mediators by monocytes and fibroblast-like synoviocytes from patients with RA.Results:hASCs suppressed the antigen-specific response of T cells from patients with RA. hASCs inhibited the proliferative response and the production of inflammatory cytokines by collagen-activated CD4 and CD8 T cells. In contrast, the numbers of IL10-producing T cells and monocytes were significantly augmented upon hASC treatment. The suppressive activity of hASCs was cell-to-cell contact dependent and independent. hASCs also stimulated the generation of FoxP3 protein-expressing CD4+CD25+ regulatory T cells, with the capacity to suppress collagen-specific T cell responses. Finally, hASCs downregulated the inflammatory response and the production of matrix-degrading enzymes by synovial cells isolated from patients with RA.Conclusions:The present work identifies hASCs as key regulators of immune tolerance, with the capacity to suppress T cell and inflammatory responses and to induce the generation/activation of antigen-specific regulatory T cells.

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Long Noncoding RNAs Regulate the Inflammatory Responses of Macrophages

Cells ◽

10.3390/cells11010005 ◽

2021 ◽

Vol 11 (1) ◽

pp. 5

Author(s):

Qing Zhao ◽

Gaozong Pang ◽

Lin Yang ◽

Shu Chen ◽

Ruiyao Xu ◽

...

Keyword(s):

Immune Responses ◽

Inflammatory Responses ◽

Inflammatory Diseases ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Innate Immune Responses ◽

Diagnostic Biomarkers ◽

Immune Balance ◽

Overwhelming Evidence ◽

Next Generation Sequencing Ngs

Long noncoding RNAs (lncRNAs) are defined as transcripts with more than 200 nucleotides that have little or no coding potential. In recent years, due to the development of next-generation sequencing (NGS), a large number of studies have revealed that lncRNAs function as key regulators to maintain immune balance and participate in diverse physiological and pathological processes in the human body. Notably, overwhelming evidence suggests that lncRNAs can regulate innate immune responses, the differentiation and development of immune cells, inflammatory autoimmune diseases, and many other immunological processes with distinct regulatory mechanisms. In this review, we summarized the emerging roles of lncRNAs in macrophage development and polarization. In addition, the potential value of lncRNAs as diagnostic biomarkers and novel therapeutic targets for the treatment of aberrant immune responses and inflammatory diseases are discussed.

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