title: Human Liver Stem Cells Suppress T-Cell Proliferation, NK Activity, and Dendritic Cell Differentiation.
abstract: Human liver stem cells (HLSCs) are a mesenchymal stromal cell-like population resident in the adult liver. Preclinical studies indicate that HLSCs could be a good candidate for cell therapy. The aim of the present study was to evaluate the immunogenicity and the immunomodulatory properties of HLSCs on T-lymphocytes, natural killer cells (NKs), and dendritic cells (DCs) in allogeneic experimental settings. We found that HLSCs inhibited T-cell proliferation by a mechanism independent of cell contact and dependent on the release of prostaglandin E2 (PGE2) and on indoleamine 2,3-dioxygenase activity. When compared with mesenchymal stromal cells (MSCs), HLSCs were more efficient in inhibiting T-cell proliferation. At variance with MSCs, HLSCs did not elicit NK degranulation. Moreover, HLSCs inhibited NK degranulation against K562, a NK-sensitive target, by a mechanism dependent on HLA-G release. When tested on DC generation from monocytes, HLSCs were found to impair DC differentiation and DCs ability to induce T-cell proliferation through PGE2. This study shows that HLSCs have immunomodulatory properties similar to MSCs, but, at variance with MSCs, they do not elicit a NK response.
authors.affiliation: Department of Molecular Biotechnology and Health Science, University of Torino, 10126 Torino, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Bruno
authors.affiliation: Department of Medical Sciences, University of Torino, 10126 Torino, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Grange
authors.affiliation: Department of Medical Sciences, University of Torino, 10126 Torino, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Tapparo
authors.affiliation: Department of Medical Sciences, University of Torino, 10126 Torino, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Pasquino
authors.affiliation: Liver Transplantation Center, University of Torino, Torino, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Romagnoli
authors.affiliation: Regional Transplantation Center, Piedmont, Molinette Hospital, Torino, Italy.
authors.forename: Ennia
authors.initials: E
authors.lastname: Dametto
authors.affiliation: Department of Medical Sciences, University of Torino, 10126 Torino, Italy; Regional Transplantation Center, Piedmont, Molinette Hospital, Torino, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Amoroso
authors.affiliation: Unicyte AG, Oberdorf, Switzerland.
authors.forename: Ciro
authors.initials: C
authors.lastname: Tetta
authors.affiliation: Department of Medical Sciences, University of Torino, 10126 Torino, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Camussi