Jag1 insufficiency alters liver fibrosis via T cell and hepatocyte differentiation defects
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F24%3A00602614" target="_blank" >RIV/68378050:_____/24:00602614 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11310/24:10489744
Result on the web
<a href="https://www.embopress.org/doi/full/10.1038/s44321-024-00145-8" target="_blank" >https://www.embopress.org/doi/full/10.1038/s44321-024-00145-8</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s44321-024-00145-8" target="_blank" >10.1038/s44321-024-00145-8</a>
Alternative languages
Result language
angličtina
Original language name
Jag1 insufficiency alters liver fibrosis via T cell and hepatocyte differentiation defects
Original language description
Fibrosis contributes to tissue repair, but excessive fibrosis disrupts organ function. Alagille syndrome (ALGS, caused by mutations in JAGGED1) results in liver disease and characteristic fibrosis. Here, we show that Jag1Ndr/Ndr mice, a model for ALGS, recapitulate ALGS-like fibrosis. Single-cell RNA-seq and multi-color flow cytometry of the liver revealed immature hepatocytes and paradoxically low intrahepatic T cell infiltration despite cholestasis in Jag1Ndr/Ndr mice. Thymic and splenic regulatory T cells (Tregs) were enriched and Jag1Ndr/Ndr lymphocyte immune and fibrotic capacity was tested with adoptive transfer into Rag1-/- mice, challenged with dextran sulfate sodium (DSS) or bile duct ligation (BDL). Transplanted Jag1Ndr/Ndr lymphocytes were less inflammatory with fewer activated T cells than Jag1+/+ lymphocytes in response to DSS. Cholestasis induced by BDL in Rag1-/- mice with Jag1Ndr/Ndr lymphocytes resulted in periportal Treg accumulation and three-fold less periportal fibrosis than in Rag1-/- mice with Jag1+/+ lymphocytes. Finally, the Jag1Ndr/Ndr hepatocyte expression profile and Treg overrepresentation were corroborated in patients' liver samples. Jag1-dependent hepatic and immune defects thus interact to determine the fibrotic process in ALGS.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10601 - Cell biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
EMBO Molecular Medicine
ISSN
1757-4676
e-ISSN
1757-4684
Volume of the periodical
16
Issue of the periodical within the volume
11
Country of publishing house
US - UNITED STATES
Number of pages
30
Pages from-to
2946-2975
UT code for WoS article
001326988900001
EID of the result in the Scopus database
2-s2.0-85205438394