Gluten-induced RNA methylation changes regulate intestinal inflammation via allele-specific XPO1 translation in epithelial cells Article Swipe
Ane Olazagoitia‐Garmendia
,
Linda Zhang
,
Paula Mera
,
J Godbout
,
Maialen Sebastian‐delaCruz
,
Iraia García‐Santisteban
,
Luis Manuel Mendoza
,
Alaín Huerta
,
Iñaki Irastorza
,
Govind Bhagat
,
Peter H. Green
,
Laura Herrero
,
Dolors Serra
,
José Antonio Rodríguez
,
Elena F. Verdú
,
Chuan He
,
José Ramón Bilbao
,
Ainara Castellanos‐Rubio
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1136/gutjnl-2020-322566
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1136/gutjnl-2020-322566
Objectives Coeliac disease (CD) is a complex autoimmune disorder that develops in genetically susceptible individuals. Dietary gluten triggers an immune response for which the only available treatment so far is a strict, lifelong gluten free diet. Human leucocyte antigen (HLA) genes and several non-HLA regions have been associated with the genetic susceptibility to CD, but their role in the pathogenesis of the disease is still essentially unknown, making it complicated to develop much needed non-dietary treatments. Here, we describe the functional involvement of a CD-associated single-nucleotide polymorphism (SNP) located in the 5’UTR of XPO1 in the inflammatory environment characteristic of the coeliac intestinal epithelium. Design The function of the CD-associated SNP was investigated using an intestinal cell line heterozygous for the SNP, N6-methyladenosine (m 6 A)-related knock-out and HLA-DQ2 mice, and human samples from patients with CD. Results Individuals harbouring the risk allele had higher m 6 A methylation in the 5’UTR of XPO1 RNA, rendering greater XPO1 protein amounts that led to downstream nuclear factor kappa B (NFkB) activity and subsequent inflammation. Furthermore, gluten exposure increased overall m 6 A methylation in humans as well as in in vitro and in vivo models. Conclusion We identify a novel m 6 A-XPO1-NFkB pathway that is activated in CD patients. The findings will prompt the development of new therapeutic approaches directed at m 6 A proteins and XPO1, a target under evaluation for the treatment of intestinal disorders.
Related Topics
Concepts
Single-nucleotide polymorphism
Coeliac disease
SNP
Biology
Methylation
Allele
Human leukocyte antigen
Gluten
Immune system
Immunology
Pathogenesis
Inflammation
Antigen
Gene
Genetics
Disease
Genotype
Medicine
Internal medicine
Food science
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1136/gutjnl-2020-322566
- https://gut.bmj.com/content/gutjnl/71/1/68.full.pdf
- OA Status
- hybrid
- Cited By
- 48
- References
- 52
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3128666375
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W3128666375Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1136/gutjnl-2020-322566Digital Object Identifier
- Title
-
Gluten-induced RNA methylation changes regulate intestinal inflammation via allele-specific XPO1 translation in epithelial cellsWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-02-01Full publication date if available
- Authors
-
Ane Olazagoitia‐Garmendia, Linda Zhang, Paula Mera, J Godbout, Maialen Sebastian‐delaCruz, Iraia García‐Santisteban, Luis Manuel Mendoza, Alaín Huerta, Iñaki Irastorza, Govind Bhagat, Peter H. Green, Laura Herrero, Dolors Serra, José Antonio Rodríguez, Elena F. Verdú, Chuan He, José Ramón Bilbao, Ainara Castellanos‐RubioList of authors in order
- Landing page
-
https://doi.org/10.1136/gutjnl-2020-322566Publisher landing page
- PDF URL
-
https://gut.bmj.com/content/gutjnl/71/1/68.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
- OA URL
-
https://gut.bmj.com/content/gutjnl/71/1/68.full.pdfDirect OA link when available
- Concepts
-
Single-nucleotide polymorphism, Coeliac disease, SNP, Biology, Methylation, Allele, Human leukocyte antigen, Gluten, Immune system, Immunology, Pathogenesis, Inflammation, Antigen, Gene, Genetics, Disease, Genotype, Medicine, Internal medicine, Food scienceTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
48Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 9, 2024: 12, 2023: 11, 2022: 12, 2021: 4Per-year citation counts (last 5 years)
- References (count)
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52Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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