HCMV infection in a mesenchymal stem cell niche: differential impact on the development of NK cells versus ILC3

Abstract: Human cytomegalovirus (HCMV) is highly prevalent in most populations worldwide and has a major influence on shaping the human immune system. Natural killer (NK) cells are important antiviral effectors that adapt to HCMV infection by expansion of virus-specific effector/memory cells. The impact of HCMV infection on the development of NK cells and innate lymphoid cells (ILC) in general is less well understood. In this context, we have recently established a novel in vitro platform to study human NK cell development in a stem cell niche based on human bone marrow-derived mesenchymal stem cells (MSC). Here, the system was modified by infecting MSC with HCMV to study the influence of virus infection on NK/ILC development. We show that cord blood-derived hematopoietic progenitor cells are successfully differentiated into mature CD56+CD94+NKG2A+ NK cells on HCMV-infected MSC with significant higher anti-viral cytokine production compared to NK cells developing on non-infected MSC. Furthermore, the generation of ILC3, characterized by expression of the signature transcription factor RAR-related orphan receptor gamma (RORγt) and the production of IL-22, was strongly impaired by HCMV infection. These observations are clinically relevant, given that ILC3 are associated with protection from graft-versus-host disease (GvHD) following stem cell transplantation and HCMV reactivation in turn is associated with increased incidence of GvHD

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch
Anmerkungen
Journal of clinical medicine. - 9, 1 (2020) , 10, ISSN: 2077-0383

Ereignis
Veröffentlichung
(wo)
Freiburg
(wer)
Universität
(wann)
2020
Urheber
Ising, Ricarda
Weinhold, Sandra
Bennstein, Sabrina Bianca
Zimmermann, Albert
Degistirici, Özer
Kögler, Gesine
Meisel, Roland
Hengel, Hartmut
Timm, Jörg
Uhrberg, Markus

DOI
10.3390/jcm9010010
URN
urn:nbn:de:bsz:25-freidok-1551453
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14.08.2025, 10:47 MESZ

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  • 2020

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