دورية أكاديمية

The co-inhibitory receptor TIGIT regulates NK cell function and is upregulated in human intrahepatic CD56 bright NK cells.

التفاصيل البيبلوغرافية
العنوان: The co-inhibitory receptor TIGIT regulates NK cell function and is upregulated in human intrahepatic CD56 bright NK cells.
المؤلفون: Ziegler AE; Research Department Virus Immunology, Leibniz Institute of Virology, Hamburg, Germany.; I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Fittje P; Research Department Virus Immunology, Leibniz Institute of Virology, Hamburg, Germany., Müller LM; Research Department Virus Immunology, Leibniz Institute of Virology, Hamburg, Germany., Ahrenstorf AE; Research Department Virus Immunology, Leibniz Institute of Virology, Hamburg, Germany., Hagemann K; Research Department Virus Immunology, Leibniz Institute of Virology, Hamburg, Germany., Hagen SH; Research Department Virus Immunology, Leibniz Institute of Virology, Hamburg, Germany., Hess LU; Research Department Virus Immunology, Leibniz Institute of Virology, Hamburg, Germany., Niehrs A; Research Department Virus Immunology, Leibniz Institute of Virology, Hamburg, Germany., Poch T; I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Ravichandran G; Institute of Experimental Immunology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Löbl SM; Research Department Virus Immunology, Leibniz Institute of Virology, Hamburg, Germany., Padoan B; Research Department Virus Immunology, Leibniz Institute of Virology, Hamburg, Germany., Brias S; Research Department Virus Immunology, Leibniz Institute of Virology, Hamburg, Germany.; I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Hennesen J; Research Department Virus Immunology, Leibniz Institute of Virology, Hamburg, Germany., Richard M; University of Bordeaux, Institut National de la Santé et de la Recherche Médicale, Bordeaux Population Health Research Center, UMR1219 and Inria, Team Statistics in systems biology and translationnal medicine (SISTM), Bordeaux, France., Richert L; University of Bordeaux, Institut National de la Santé et de la Recherche Médicale, Bordeaux Population Health Research Center, UMR1219 and Inria, Team Statistics in systems biology and translationnal medicine (SISTM), Bordeaux, France., Peine S; Institute for Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Oldhafer KJ; Department of General and Abdominal Surgery, Asklepios Hospital Barmbek, Semmelweis University of Medicine, Hamburg, Germany., Fischer L; Department of Visceral Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Schramm C; I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Martin Zeitz Centre for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Martrus G; Research Department Virus Immunology, Leibniz Institute of Virology, Hamburg, Germany., Bunders MJ; Research Department Virus Immunology, Leibniz Institute of Virology, Hamburg, Germany.; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Altfeld M; Research Department Virus Immunology, Leibniz Institute of Virology, Hamburg, Germany., Lunemann S; Research Department Virus Immunology, Leibniz Institute of Virology, Hamburg, Germany.
المصدر: Frontiers in immunology [Front Immunol] 2023 Feb 09; Vol. 14, pp. 1117320. Date of Electronic Publication: 2023 Feb 09 (Print Publication: 2023).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Lausanne : Frontiers Research Foundation]
مواضيع طبية MeSH: Killer Cells, Natural*/metabolism , Liver*/metabolism, Humans ; CD56 Antigen/metabolism ; Receptors, Immunologic/genetics ; Receptors, Immunologic/metabolism ; Flow Cytometry
مستخلص: The crosstalk between NK cells and their surrounding environment is enabled through activating and inhibitory receptors, which tightly control NK cell activity. The co-inhibitory receptor TIGIT decreases NK cell cytotoxicity and is involved in NK cell exhaustion, but has also been associated with liver regeneration, highlighting that the contribution of human intrahepatic CD56 bright NK cells in regulating tissue homeostasis remains incompletely understood. A targeted single-cell mRNA analysis revealed distinct transcriptional differences between matched human peripheral blood and intrahepatic CD56 bright NK cells. Multiparameter flow cytometry identified a cluster of intrahepatic NK cells with overlapping high expression of CD56, CD69, CXCR6, TIGIT and CD96. Intrahepatic CD56 bright NK cells also expressed significantly higher protein surface levels of TIGIT, and significantly lower levels of DNAM-1 compared to matched peripheral blood CD56 bright NK cells. TIGIT + CD56 bright NK cells showed diminished degranulation and TNF-α production following stimulation. Co-incubation of peripheral blood CD56 bright NK cells with human hepatoma cells or primary human hepatocyte organoids resulted in migration of NK cells into hepatocyte organoids and upregulation of TIGIT and downregulation of DNAM-1 expression, in line with the phenotype of intrahepatic CD56 bright NK cells. Intrahepatic CD56 bright NK cells represent a transcriptionally, phenotypically, and functionally distinct population of NK cells that expresses higher levels of TIGIT and lower levels of DNAM-1 than matched peripheral blood CD56 bright NK cells. Increased expression of inhibitory receptors by NK cells within the liver environment can contribute to tissue homeostasis and reduction of liver inflammation.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Ziegler, Fittje, Müller, Ahrenstorf, Hagemann, Hagen, Hess, Niehrs, Poch, Ravichandran, Löbl, Padoan, Brias, Hennesen, Richard, Richert, Peine, Oldhafer, Fischer, Schramm, Martrus, Bunders, Altfeld and Lunemann.)
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فهرسة مساهمة: Keywords: DNAM-1; PVR/CD155; TIGIT; immune tolerance; intrahepatic NK cells; liver organoids; single-cell mRNA analysis; tissue homeostasis
المشرفين على المادة: 0 (CD56 Antigen)
0 (Receptors, Immunologic)
0 (TIGIT protein, human)
تواريخ الأحداث: Date Created: 20230227 Date Completed: 20230228 Latest Revision: 20240314
رمز التحديث: 20240315
مُعرف محوري في PubMed: PMC9948018
DOI: 10.3389/fimmu.2023.1117320
PMID: 36845105
قاعدة البيانات: MEDLINE
الوصف
تدمد:1664-3224
DOI:10.3389/fimmu.2023.1117320