Celiac disease (CD) is an autoimmune enteropathy arising in genetically predisposed subjects exposed to gluten, which activates both innate and adaptive immunity. Although the pathogenesis is common to all patients, the clinical spectrum is quite variable, and differences could be explained by gene expression variations. Among the factors able to affect gene expression, there are lncRNAs. We evaluated the expression profile of 87 lncRNAs in CD vs. healthy control (HC) intestinal biopsies by RT-qPCR array. Nuclear enriched abundant transcript 1 (NEAT1) and taurine upregulated gene 1 (TUG1) were detected as downregulated in CD patients at diagnosis, but their expression increased in biopsies of patients on a gluten-free diet (GFD) exposed to gluten. The increase in NEAT1 expression after gluten exposure was mediated by IL-15 and STAT3 activation and binding to the NEAT1 promoter, as demonstrated by gel shift assay. NEAT1 is localized in the nucleus and can regulate gene expression by sequestering transcription factors, and it has been implicated in immune regulation and control of cell proliferation. The demonstration of its regulation by gluten thus also supports the role of lncRNAs in CD and prompts further research on these RNAs as gene expression regulators.

Gnodi, E., Mancuso, C., Elli, L., Ballarini, E., Meneveri, R., Beaulieu, J., et al. (2021). Gliadin, through the Activation of Innate Immunity, Triggers lncRNA NEAT1 Expression in Celiac Disease Duodenal Mucosa. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22(3), 1-15 [10.3390/ijms22031289].

Gliadin, through the Activation of Innate Immunity, Triggers lncRNA NEAT1 Expression in Celiac Disease Duodenal Mucosa

Gnodi, Elisa;Mancuso, Clara;Ballarini, Elisa;Meneveri, Raffaella;Barisani, Donatella
2021

Abstract

Celiac disease (CD) is an autoimmune enteropathy arising in genetically predisposed subjects exposed to gluten, which activates both innate and adaptive immunity. Although the pathogenesis is common to all patients, the clinical spectrum is quite variable, and differences could be explained by gene expression variations. Among the factors able to affect gene expression, there are lncRNAs. We evaluated the expression profile of 87 lncRNAs in CD vs. healthy control (HC) intestinal biopsies by RT-qPCR array. Nuclear enriched abundant transcript 1 (NEAT1) and taurine upregulated gene 1 (TUG1) were detected as downregulated in CD patients at diagnosis, but their expression increased in biopsies of patients on a gluten-free diet (GFD) exposed to gluten. The increase in NEAT1 expression after gluten exposure was mediated by IL-15 and STAT3 activation and binding to the NEAT1 promoter, as demonstrated by gel shift assay. NEAT1 is localized in the nucleus and can regulate gene expression by sequestering transcription factors, and it has been implicated in immune regulation and control of cell proliferation. The demonstration of its regulation by gluten thus also supports the role of lncRNAs in CD and prompts further research on these RNAs as gene expression regulators.
Articolo in rivista - Articolo scientifico
Celiac disease; Innate immunity; Long non-coding RNAs; NEAT1; TUG1;
English
28-gen-2021
2021
22
3
1
15
1289
open
Gnodi, E., Mancuso, C., Elli, L., Ballarini, E., Meneveri, R., Beaulieu, J., et al. (2021). Gliadin, through the Activation of Innate Immunity, Triggers lncRNA NEAT1 Expression in Celiac Disease Duodenal Mucosa. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22(3), 1-15 [10.3390/ijms22031289].
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