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Verfasst von:Kurt, Ada S. [VerfasserIn]   i
 Strobl, Karoline [VerfasserIn]   i
 Ruiz, Paula [VerfasserIn]   i
 Osborn, Gabriel [VerfasserIn]   i
 Chester, Tonika [VerfasserIn]   i
 Dawson, Lauren [VerfasserIn]   i
 Warwas, Karsten M. [VerfasserIn]   i
 Grey, Elizabeth H. [VerfasserIn]   i
 Mastoridis, Sotiris [VerfasserIn]   i
 Kodela, Elisavet [VerfasserIn]   i
 Safinia, Niloufar [VerfasserIn]   i
 Sanchez-Fueyo, Alberto [VerfasserIn]   i
 Martinez-Llordella, Marc [VerfasserIn]   i
Titel:IL-2 availability regulates the tissue specific phenotype of murine intra-hepatic Tregs
Verf.angabe:Ada S. Kurt, Karoline Strobl, Paula Ruiz, Gabriel Osborn, Tonika Chester, Lauren Dawson, Karsten M. Warwas, Elizabeth H. Grey, Sotiris Mastoridis, Elisavet Kodela, Niloufar Safinia, Alberto Sanchez-Fueyo and Marc Martinez-Llordella
E-Jahr:2022
Jahr:31 October 2022
Umfang:14 S.
Fussnoten:Gesehen am 12.01.2023
Titel Quelle:Enthalten in: Frontiers in immunology
Ort Quelle:Lausanne : Frontiers Media, 2010
Jahr Quelle:2022
Band/Heft Quelle:13(2022), Artikel-ID 1040031, Seite 1-14
ISSN Quelle:1664-3224
Abstract:CD4+CD25+Foxp3+ Tregs are known to acquire tissue-specific features and exert cytoprotective and regenerative functions. The extent to which this applies to liver-resident Tregs is unknown. In this study, we aimed to explore the phenotypic and functional characteristics of adult murine liver resident Tregs during homeostasis. Additionally, we investigated their role in ameliorating liver inflammation and tissue damage. Quantification of Foxp3+CD4+CD25+ cells comparing different tissues showed that the liver contained significantly fewer resident Tregs. A combination of flow cytometry phenotyping and microarray analysis of intra-hepatic and splenic Tregs under homeostatic conditions revealed that, although intra-hepatic Tregs exhibited the core transcriptional Treg signature, they expressed a distinct transcriptional profile. This was characterized by reduced CD25 expression and increased levels of pro-inflammatory Th1 transcripts Il1b and Ifng. In vivo ablation of Tregs in the Foxp3-DTR mouse model showed that Tregs had a role in reducing the magnitude of systemic and intra-hepatic inflammatory responses following acute carbon tetrachloride (CCl₄) injury, but their absence did not impact the development of hepatocyte necrosis. Conversely, the specific expansion of Tregs by administration of IL-2 complexes increased the number of intra-hepatic Tregs and significantly ameliorated tissue damage following CCl₄ administration in C57BL/6 mice. The cytoprotective effect observed in response to IL-2c was associated with the increased expression of markers known to regulate Treg suppressive function. Our results offer insight into the transcriptome and complex immune network of intra-hepatic Tregs and suggest that strategies capable of selectively increasing the pool of intra-hepatic Tregs could constitute effective therapies in inflammatory liver diseases.
DOI:doi:10.3389/fimmu.2022.1040031
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.3389/fimmu.2022.1040031
 Volltext: https://www.frontiersin.org/articles/10.3389/fimmu.2022.1040031
 DOI: https://doi.org/10.3389/fimmu.2022.1040031
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1830900722
Verknüpfungen:→ Zeitschrift

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