A long noncoding RNA associated with susceptibility to celiac disease

Castellanos–Rubio, Ainara; Fernández-Jiménez, Nora; Kratchmarov, Radomir; Luo, Xi; Bhagat, Govind; Green, Peter H. R.; Schneider, Robert J.; Kiledjian, Megerditch; Bilbao, José Ramón; Ghosh, Sankar

doi:10.1126/science.aad0467

Cited by 218 publications

(184 citation statements)

References 34 publications

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“…Knockdown of IL1␤-eRNA and IL1␤-RBT46 together in activated cells specifically reduces the mRNA and protein levels of IL1-␤ and CXCL8, complying with their functional archetype as eRNAs (43,48,49).…”

Section: Lncrnas As Enhancers Of the Inflammatory Responsementioning

confidence: 83%

“…Through NF-B signaling, lincRNA-Cox2, AS-IL1␣, and PACER (p50-associated COX-2 extragenic RNA) are up-regulated in macrophages upon ligation of numerous TLRs, including TLR4 by LPS (26,46,47). Similarly, IL1␤-eRNA, IL1␤-RBT46, and lnc13 are induced in human monocytes and macrophages in response to LPS through NF-B signaling (48,49). NF-B-interacting lncRNA (NKILA) is highly induced in response to IL-1␤ and TNF-␣ stimulation (50).…”

Section: Lncrnas Models Of Transcriptional Control and Expression Inmentioning

confidence: 99%

“…Similar to Lethe, NKILA has been found to restrain NF-B-driven inflammation. NKILA can mask the phosphorylation motifs of IB to block IB degradation, and thus it prevents the translocation of NF-B to the nucleus, representing a class of lncRNAs that are able to regulate gene expression via post-translational modification of signaling proteins (49). Interestingly, lincRNA-p21 has been found to sequester p65 mRNA and thus attenuates the translation of p65, resulting in inhibition of basal and TNF-␣-stimulated NF-B activity, as measured by phospho-p65 (56).…”

Section: Lncrnas As Suppressors Of the Inflammatory Responsementioning

confidence: 99%

“…lnc13 has been implicated in celiac disease, a chronic, immunemediated intestinal disorder that is triggered by ingested gluten (70). Levels of lnc13 are significantly down-regulated in samples from patients afflicted with celiac disease compared with control, suggesting that its down-regulation may be a contributing factor to the underlying inflammation in this disease (49).…”

Section: Lncrnas and Pathogenesis Of Inflammatory Diseasementioning

confidence: 99%

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Long non-coding RNAs (lncRNAs) and their transcriptional control of inflammatory responses

Mathy

Chen

2017

Journal of Biological Chemistry

213

162

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Edited by George M. Carman Long non-coding RNAs (lncRNAs) have emerged as potential key regulators of the inflammatory response, particularly by modulating the transcriptional control of inflammatory genes. lncRNAs may act as an enhancer or suppressor to inflammatory transcription, function as scaffold molecules through interactions with RNA-binding proteins in chromatin remodeling complexes, and modulate dynamic and epigenetic control of inflammatory transcription in a gene-specific and time-dependent fashion. Here, we will review recent literature regarding the role of lncRNAs in transcriptional control of inflammatory responses. Better understanding of lncRNA regulation of inflammation will provide novel targets for the development of new therapeutic strategies.Because of the potentially destructive nature of the inflammatory response, the expression of inflammation-related genes is finely regulated at multiple levels, including transcription, mRNA processing, translation, phosphorylation, and degradation. Transcription represents an essential, and often the most important, regulatory determinant of the inflammation process. Many signaling pathways and transcription factors are involved in the inflammatory response, including the transcription factor nuclear factor-B (NF-B), 2 MAPK, and JAK/ STAT pathways, together controlling a multitude of inflammatory response genes (1, 2). Upon activation, these pathways directly activate and induce the expression of a limited set of transcription factors that promote the transcription of inflammatory genes. Whereas the mechanisms of initial activation and subsequent nuclear translocation of associated transcription factors for these signaling pathways are well-characterized, how the transcription of inflammatory genes is finely controlled in the nucleus to ensure that each individual gene is transcribed at the "right" place at the "right" time remains elusive. Perhaps this can be best represented by the inflammatory transcription induced by NF-B. The NF-B signaling cascade can be activated by inflammatory signals, including LPS, TNF-␣, IL-1␤, and reactive oxygen species, among others; many Toll-like receptors (TLRs) also activate NF-B (3-8).Prior to an activating signal, NF-B dimers are sequestered in the cytoplasm and held inactive by association with I B proteins (9). Activating stimuli cause I B degradation (10, 11), and consequently, free NF-B dimers translocate to the nucleus, bind to B sites, and promote gene transcription (12). Common targets of NF-B include inflammatory cytokines, chemokines, adhesion molecules, cytoprotective proteins, and proteins regulating cell differentiation, proliferation, and survival (13,14). In addition to its initial cytoplasmic activation, both the recruitment of NF-B to target genes in the nuclei and NF-B-induced transcriptional events after recruitment are finely controlled events to ensure proper transactivation of NF-B target genes (15). Indeed, several waves of gene transcription have been demonstrated in macrophages following LP...

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Section: Lncrnas As Enhancers Of the Inflammatory Responsementioning

confidence: 83%

Section: Lncrnas Models Of Transcriptional Control and Expression Inmentioning

confidence: 99%

Section: Lncrnas As Suppressors Of the Inflammatory Responsementioning

confidence: 99%

Section: Lncrnas and Pathogenesis Of Inflammatory Diseasementioning

confidence: 99%

See 2 more Smart Citations

Long non-coding RNAs (lncRNAs) and their transcriptional control of inflammatory responses

Mathy

Chen

2017

Journal of Biological Chemistry

213

162

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“…Some lncRNAs are dynamically expressed during development (33), and others are important for granulocyte homeostasis (e.g., Morrbid regulates myeloid cell lifespan) (34) or immune effector functions (e.g., Rmrp and Th17 cell function, NeST and IFNγ expression in T cells) (35,36). Consequently, lncRNAs influence the immunopathology of infections (NeST, Morrbid), endotoxic shock (lincRNA-EPS) (37), or gut inflammatory diseases (Rmrp, linc-13) (36,38).…”

Section: R Egulatory T Cells (Tregs) a Subset Of Cd4 + T Cells Determentioning

confidence: 99%

Flicr , a long noncoding RNA, modulates Foxp3 expression and autoimmunity

Zemmour

Pratama

Loughhead

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

140

102

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A combination of transcription factors, enhancers, and epigenetic marks determines the expression of the key transcription factor FoxP3 in regulatory T cells (Tregs). Adding an additional layer of complexity, the long noncoding RNA (lncRNA) Flicr (Foxp3 long intergenic noncoding RNA) is a negative regulator that tunes Foxp3 expression, resulting in a subset of Tregs with twofold-to fivefoldlower levels of FoxP3 protein. The impact of Flicr is particularly marked in conditions of IL-2 deficiency, and, conversely, IL-2 represses Flicr expression. Flicr neighbors Foxp3 in mouse and human genomes, is specifically expressed in mature Tregs, and acts only in cis. It does not affect DNA methylation, but modifies chromatin accessibility in the conserved noncoding sequence 3 (CNS3)/Accessible region 5 (AR5) region of Foxp3. Like many lncRNAs, Flicr's molecular effects are subtle, but by curtailing Treg activity, Flicr markedly promotes autoimmune diabetes and, conversely, restrains antiviral responses. This mechanism of FoxP3 control may allow escape from dominant Treg control during infection or cancer, at the cost of heightened autoimmunity.autoimmunity | regulatory T cells | gene regulation | long noncoding RNA | Foxp3

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Long noncoding RNAs as regulators of cancer immunity

2018

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Long noncoding RNAs (lncRNAs) are increasingly known to be important in cancer as they directly interact with the cell cycle, proliferation pathways and microbiome balance. Moreover, lncRNAs regulate the immune system: they do not directly encode proteins of innate or adaptive immunity, but regulate immune cell differentiation and function, such as dendritic cell activity, T cell ratio and metabolism. The result of this complex interaction is that lncRNAs regulate cancer processes through a complex multimodal system involving immunity, metabolism and infection. The possible functions of lncRNAs and their roles in the regulation of cancer immunity will be reported and discussed in the present review. Recent studies showed their function as regulators in the tumour microenvironment (TME), epithelial–mesenchymal transition, microbiota, metabolism and immune cell differentiation. However, there is not much knowledge regarding their roles in cancer immunity regulation. Thus, the main aim of this review is to describe lncRNAs that have specifically been associated with immunity, the immune cycle and the TME.

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A long noncoding RNA associated with susceptibility to celiac disease

Cited by 218 publications

References 34 publications

Long non-coding RNAs (lncRNAs) and their transcriptional control of inflammatory responses

Long non-coding RNAs (lncRNAs) and their transcriptional control of inflammatory responses

Flicr , a long noncoding RNA, modulates Foxp3 expression and autoimmunity

Long noncoding RNAs as regulators of cancer immunity

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