Interleukin-22 orchestrates a pathological endoplasmic reticulum stress response transcriptional programme in colonic epithelial cells Article Swipe
Nick Powell
,
Eirini Pantazi
,
Polychronis Pavlidis
,
Anastasia Tsakmaki
,
Katherine Li
,
Feifei Yang
,
Aimée Parker
,
Carmen Pin
,
Domenico Cozzetto
,
Danielle Minns
,
Émilie Stolarczyk
,
Svetlana Saveljeva
,
Rami Mohamed
,
Paul Lavender
,
Behdad Afzali
,
Jonathan Digby‐Bell
,
Tsui Tjir-Li
,
Arthur Kaser
,
Joshua R. Friedman
,
Thomas T. MacDonald
,
Gavin A. Bewick
,
Graham M. Lord
·
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1136/gutjnl-2019-318483
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.1136/gutjnl-2019-318483
Objective The functional role of interleukin-22 (IL22) in chronic inflammation is controversial, and mechanistic insights into how it regulates target tissue are lacking. In this study, we evaluated the functional role of IL22 in chronic colitis and probed mechanisms of IL22-mediated regulation of colonic epithelial cells. Design To investigate the functional role of IL22 in chronic colitis and how it regulates colonic epithelial cells, we employed a three-dimentional mini-gut epithelial organoid system, in vivo disease models and transcriptomic datasets in human IBD. Results As well as inducing transcriptional modules implicated in antimicrobial responses, IL22 also coordinated an endoplasmic reticulum (ER) stress response transcriptional programme in colonic epithelial cells. In the colon of patients with active colonic Crohn’s disease (CD), there was enrichment of IL22-responsive transcriptional modules and ER stress response modules. Strikingly, in an IL22-dependent model of chronic colitis, targeting IL22 alleviated colonic epithelial ER stress and attenuated colitis. Pharmacological modulation of the ER stress response similarly impacted the severity of colitis. In patients with colonic CD, antibody blockade of IL12p40, which simultaneously blocks IL12 and IL23, the key upstream regulator of IL22 production, alleviated the colonic epithelial ER stress response. Conclusions Our data challenge perceptions of IL22 as a predominantly beneficial cytokine in IBD and provide novel insights into the molecular mechanisms of IL22-mediated pathogenicity in chronic colitis. Targeting IL22-regulated pathways and alleviating colonic epithelial ER stress may represent promising therapeutic strategies in patients with colitis. Trial registration number NCT02749630 .
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Metadata
- Type
- review
- Language
- en
- Landing Page
- https://doi.org/10.1136/gutjnl-2019-318483
- https://gut.bmj.com/content/gutjnl/69/3/578.full.pdf
- OA Status
- hybrid
- Cited By
- 140
- References
- 49
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2996481293
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W2996481293Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1136/gutjnl-2019-318483Digital Object Identifier
- Title
-
Interleukin-22 orchestrates a pathological endoplasmic reticulum stress response transcriptional programme in colonic epithelial cellsWork title
- Type
-
reviewOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2019Year of publication
- Publication date
-
2019-12-02Full publication date if available
- Authors
-
Nick Powell, Eirini Pantazi, Polychronis Pavlidis, Anastasia Tsakmaki, Katherine Li, Feifei Yang, Aimée Parker, Carmen Pin, Domenico Cozzetto, Danielle Minns, Émilie Stolarczyk, Svetlana Saveljeva, Rami Mohamed, Paul Lavender, Behdad Afzali, Jonathan Digby‐Bell, Tsui Tjir-Li, Arthur Kaser, Joshua R. Friedman, Thomas T. MacDonald, Gavin A. Bewick, Graham M. LordList of authors in order
- Landing page
-
https://doi.org/10.1136/gutjnl-2019-318483Publisher landing page
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https://gut.bmj.com/content/gutjnl/69/3/578.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
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-
https://gut.bmj.com/content/gutjnl/69/3/578.full.pdfDirect OA link when available
- Concepts
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Interleukin 22, Colitis, Unfolded protein response, Inflammatory bowel disease, Endoplasmic reticulum, Inflammation, Immunology, Biology, Medicine, Cytokine, Interleukin, Cell biology, Pathology, DiseaseTop concepts (fields/topics) attached by OpenAlex
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140Total citation count in OpenAlex
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2025: 17, 2024: 40, 2023: 17, 2022: 30, 2021: 20Per-year citation counts (last 5 years)
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49Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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