Cargando…
Liver mesenchymal stem cells are superior inhibitors of NK cell functions through differences in their secretome compared to other mesenchymal stem cells
Liver-resident mesenchymal stem cells (L-MSCs) are superior inhibitors of alloreactive T cell responses compared to their counterparts from bone marrow (BM-MSCs) or adipose tissue (A-MSCs), suggesting a role in liver’s overall tolerogenic microenvironment. Whether L-MSCs also impact NK cell function...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9534521/ https://www.ncbi.nlm.nih.gov/pubmed/36211345 http://dx.doi.org/10.3389/fimmu.2022.952262 |
_version_ | 1784802560717094912 |
---|---|
author | Yigitbilek, Furkan Ozdogan, Elif Abrol, Nitin Park, Walter D. Hansen, Michael J. Dasari, Surendra Stegall, Mark D. Taner, Timucin |
author_facet | Yigitbilek, Furkan Ozdogan, Elif Abrol, Nitin Park, Walter D. Hansen, Michael J. Dasari, Surendra Stegall, Mark D. Taner, Timucin |
author_sort | Yigitbilek, Furkan |
collection | PubMed |
description | Liver-resident mesenchymal stem cells (L-MSCs) are superior inhibitors of alloreactive T cell responses compared to their counterparts from bone marrow (BM-MSCs) or adipose tissue (A-MSCs), suggesting a role in liver’s overall tolerogenic microenvironment. Whether L-MSCs also impact NK cell functions differently than other MSCs is not known. We generated and characterized L-MSCs, A-MSCs and BM-MSCs from human tissues. The mass spectrometry analysis demonstrated that L-MSC secretome is uniquely different than that of A-MSC/BM-MSC, with enriched protein sets involved in IFNγ responses and signaling. When co-cultured with primary human NK cells, L-MSCs but not other MSCs, decreased surface expression of activating receptors NKp44 and NKG2D. L-MSCs also decreased IFNγ secretion by IL-2-stimulated NK cells more effectively than other MSCs. Cytolytic function of NK cells were reduced significantly when co-cultured with L-MSCs, whereas A-MSCs or BM-MSCs did not have a major impact. Mechanistic studies showed that the L-MSC-mediated reduction in NK cell cytotoxicity is not through changes in secretion of the cytotoxic proteins Perforin, Granzyme A or B, but through increased production of HLA-C1 found in L-MSC secretome that inhibits NK cells by stimulating their inhibitory receptor KIRDL2/3. L-MSCs are more potent inhibitors of NK cell functions than A-MSC or BM-MSC. Combined with their T cell inhibitory features, these results suggest L-MSCs contribute to the tolerogenic liver microenvironment and liver-induced systemic tolerance often observed after liver transplantation. |
format | Online Article Text |
id | pubmed-9534521 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95345212022-10-06 Liver mesenchymal stem cells are superior inhibitors of NK cell functions through differences in their secretome compared to other mesenchymal stem cells Yigitbilek, Furkan Ozdogan, Elif Abrol, Nitin Park, Walter D. Hansen, Michael J. Dasari, Surendra Stegall, Mark D. Taner, Timucin Front Immunol Immunology Liver-resident mesenchymal stem cells (L-MSCs) are superior inhibitors of alloreactive T cell responses compared to their counterparts from bone marrow (BM-MSCs) or adipose tissue (A-MSCs), suggesting a role in liver’s overall tolerogenic microenvironment. Whether L-MSCs also impact NK cell functions differently than other MSCs is not known. We generated and characterized L-MSCs, A-MSCs and BM-MSCs from human tissues. The mass spectrometry analysis demonstrated that L-MSC secretome is uniquely different than that of A-MSC/BM-MSC, with enriched protein sets involved in IFNγ responses and signaling. When co-cultured with primary human NK cells, L-MSCs but not other MSCs, decreased surface expression of activating receptors NKp44 and NKG2D. L-MSCs also decreased IFNγ secretion by IL-2-stimulated NK cells more effectively than other MSCs. Cytolytic function of NK cells were reduced significantly when co-cultured with L-MSCs, whereas A-MSCs or BM-MSCs did not have a major impact. Mechanistic studies showed that the L-MSC-mediated reduction in NK cell cytotoxicity is not through changes in secretion of the cytotoxic proteins Perforin, Granzyme A or B, but through increased production of HLA-C1 found in L-MSC secretome that inhibits NK cells by stimulating their inhibitory receptor KIRDL2/3. L-MSCs are more potent inhibitors of NK cell functions than A-MSC or BM-MSC. Combined with their T cell inhibitory features, these results suggest L-MSCs contribute to the tolerogenic liver microenvironment and liver-induced systemic tolerance often observed after liver transplantation. Frontiers Media S.A. 2022-09-21 /pmc/articles/PMC9534521/ /pubmed/36211345 http://dx.doi.org/10.3389/fimmu.2022.952262 Text en Copyright © 2022 Yigitbilek, Ozdogan, Abrol, Park, Hansen, Dasari, Stegall and Taner https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Yigitbilek, Furkan Ozdogan, Elif Abrol, Nitin Park, Walter D. Hansen, Michael J. Dasari, Surendra Stegall, Mark D. Taner, Timucin Liver mesenchymal stem cells are superior inhibitors of NK cell functions through differences in their secretome compared to other mesenchymal stem cells |
title | Liver mesenchymal stem cells are superior inhibitors of NK cell functions through differences in their secretome compared to other mesenchymal stem cells |
title_full | Liver mesenchymal stem cells are superior inhibitors of NK cell functions through differences in their secretome compared to other mesenchymal stem cells |
title_fullStr | Liver mesenchymal stem cells are superior inhibitors of NK cell functions through differences in their secretome compared to other mesenchymal stem cells |
title_full_unstemmed | Liver mesenchymal stem cells are superior inhibitors of NK cell functions through differences in their secretome compared to other mesenchymal stem cells |
title_short | Liver mesenchymal stem cells are superior inhibitors of NK cell functions through differences in their secretome compared to other mesenchymal stem cells |
title_sort | liver mesenchymal stem cells are superior inhibitors of nk cell functions through differences in their secretome compared to other mesenchymal stem cells |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9534521/ https://www.ncbi.nlm.nih.gov/pubmed/36211345 http://dx.doi.org/10.3389/fimmu.2022.952262 |
work_keys_str_mv | AT yigitbilekfurkan livermesenchymalstemcellsaresuperiorinhibitorsofnkcellfunctionsthroughdifferencesintheirsecretomecomparedtoothermesenchymalstemcells AT ozdoganelif livermesenchymalstemcellsaresuperiorinhibitorsofnkcellfunctionsthroughdifferencesintheirsecretomecomparedtoothermesenchymalstemcells AT abrolnitin livermesenchymalstemcellsaresuperiorinhibitorsofnkcellfunctionsthroughdifferencesintheirsecretomecomparedtoothermesenchymalstemcells AT parkwalterd livermesenchymalstemcellsaresuperiorinhibitorsofnkcellfunctionsthroughdifferencesintheirsecretomecomparedtoothermesenchymalstemcells AT hansenmichaelj livermesenchymalstemcellsaresuperiorinhibitorsofnkcellfunctionsthroughdifferencesintheirsecretomecomparedtoothermesenchymalstemcells AT dasarisurendra livermesenchymalstemcellsaresuperiorinhibitorsofnkcellfunctionsthroughdifferencesintheirsecretomecomparedtoothermesenchymalstemcells AT stegallmarkd livermesenchymalstemcellsaresuperiorinhibitorsofnkcellfunctionsthroughdifferencesintheirsecretomecomparedtoothermesenchymalstemcells AT tanertimucin livermesenchymalstemcellsaresuperiorinhibitorsofnkcellfunctionsthroughdifferencesintheirsecretomecomparedtoothermesenchymalstemcells |