The type 1 diabetes gene TYK2 regulates β-cell development and its responses to interferon-α Article Swipe
Vikash Chandra
,
Hazem Ibrahim
,
Clémentine Halliez
,
Rashmi B. Prasad
,
Federica Vecchio
,
Om Prakash Dwivedi
,
Jouni Kvist
,
Diego Balboa
,
Jonna Saarimäki‐Vire
,
Hossam Montaser
,
Tom Barsby
,
Väinö Lithovius
,
Isabella Artner
,
Swetha Gopalakrishnan
,
Leif Groop
,
Roberto Mallone
,
Décio L. Eizirik
,
Timo Otonkoski
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1101/2022.02.22.481272
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1101/2022.02.22.481272
Type 1 diabetes (T1D) is an autoimmune disease that results in the destruction of insulin producing pancreatic β-cells. One of the genes associated with T1D is TYK2, which encodes a Janus kinase with critical roles in type-Ι interferon (IFN) mediated intracellular signaling. To study the role of TYK2 in human pancreatic β-cell development and response to IFNα, we generated TYK2 knockout human iPSCs and directed them into the pancreatic endocrine lineage. Here we show that loss of TYK2 compromised the emergence of endocrine precursors by regulating KRAS expression while mature stem cell-islets (SC-islets) function was not affected. In the maturing SC-islets, the loss or inhibition of TYK2 prevented IFNα-induced antigen processing and presentation, including MHC Class Ι expression in pancreatic endocrine and progenitor cells. Furthermore, in a CD8 + cytotoxic T-cell co-culture model, the survival of β-cells was enhanced by a selective TYK2 inhibitor. These results identify an unsuspected role for TYK2 on β-cell development and support TYK2 inhibition in adult β-cells as a potent therapeutic target to halt T1D progression.
Related Topics
Concepts
Tyrosine kinase 2
Pancreatic islets
Biology
Interferon
Cancer research
Cell biology
Progenitor cell
Enteroendocrine cell
NOD mice
CD8
Stem cell
Endocrinology
Immunology
Islet
Immune system
Receptor
Insulin
Endocrine system
Genetics
Hormone
Growth factor
Platelet-derived growth factor receptor
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2022.02.22.481272
- https://www.biorxiv.org/content/biorxiv/early/2022/02/22/2022.02.22.481272.full.pdf
- OA Status
- green
- References
- 49
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4212784271
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4212784271Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1101/2022.02.22.481272Digital Object Identifier
- Title
-
The type 1 diabetes gene TYK2 regulates β-cell development and its responses to interferon-αWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-02-22Full publication date if available
- Authors
-
Vikash Chandra, Hazem Ibrahim, Clémentine Halliez, Rashmi B. Prasad, Federica Vecchio, Om Prakash Dwivedi, Jouni Kvist, Diego Balboa, Jonna Saarimäki‐Vire, Hossam Montaser, Tom Barsby, Väinö Lithovius, Isabella Artner, Swetha Gopalakrishnan, Leif Groop, Roberto Mallone, Décio L. Eizirik, Timo OtonkoskiList of authors in order
- Landing page
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https://doi.org/10.1101/2022.02.22.481272Publisher landing page
- PDF URL
-
https://www.biorxiv.org/content/biorxiv/early/2022/02/22/2022.02.22.481272.full.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
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https://www.biorxiv.org/content/biorxiv/early/2022/02/22/2022.02.22.481272.full.pdfDirect OA link when available
- Concepts
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Tyrosine kinase 2, Pancreatic islets, Biology, Interferon, Cancer research, Cell biology, Progenitor cell, Enteroendocrine cell, NOD mice, CD8, Stem cell, Endocrinology, Immunology, Islet, Immune system, Receptor, Insulin, Endocrine system, Genetics, Hormone, Growth factor, Platelet-derived growth factor receptorTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
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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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