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@article{1786891,
author = {Tidu, Federico and De Zuani, Marco and Jose, Shyam Sushama and Bendickova, Kamila and Kubala, Lukáš and Caruso, Frank and Cavalieri, Francesca and Forte, Giancarlo and Frič, Jan},
article_location = {CAMBRIDGE},
article_number = {6},
doi = {http://dx.doi.org/10.1016/j.isci.2021.102683},
keywords = {NFAT signaling; human mesenchymal stromal cells},
language = {eng},
issn = {2589-0042},
journal = {iSCIENCE},
title = {NFAT signaling in human mesenchymal stromal cells affects extracellular matrix remodeling and antifungal immune responses},
url = {https://www.sciencedirect.com/science/article/pii/S2589004221006519?via%3Dihub},
volume = {24},
year = {2021}
}
TY - JOUR
ID - 1786891
AU - Tidu, Federico - De Zuani, Marco - Jose, Shyam Sushama - Bendickova, Kamila - Kubala, Lukáš - Caruso, Frank - Cavalieri, Francesca - Forte, Giancarlo - Frič, Jan
PY - 2021
TI - NFAT signaling in human mesenchymal stromal cells affects extracellular matrix remodeling and antifungal immune responses
JF - iSCIENCE
VL - 24
IS - 6
SP - 1-24
EP - 1-24
PB - CELL PRESS
SN - 25890042
KW - NFAT signaling
KW - human mesenchymal stromal cells
UR - https://www.sciencedirect.com/science/article/pii/S2589004221006519?via%3Dihub
N2 - Mesenchymal stromal cells (MSCs) combined with calcineurin-nuclear factor of activated T cell (CN-NFAT) inhibitors are being tested as a treatment for graft-versus-host disease (GvHD). The immunosuppressive properties of MSCs seem beneficial; however, their response during fungal infection, which is an important cause of mortality in patients with GvHD, is unknown. We report that MSCs phagocytose the fungal component zymosan, resulting in phosphorylation of spleen tyrosine kinase (Syk), increase in cytosolic calcium levels, and ultimately, increase in NFAT1 nuclear translocation. RNA sequencing analysis of zymosan-treated MSCs showed that CN-NFAT inhibition affects extracellular matrix (ECM) genes but not cytokine expression that is under the control of the NF-kappa B pathway. When coculturing MSCs or decellularized MSC-ECM with human peripheral blood mononuclear cells (PBMCs), selective NFAT inhibition in MSCs decreased cytokine expression by PBMCs. These findings reveal a dual mechanism underlying the MSC response to zymosan: while NF-kappa B directly controls inflammatory cytokine expression, NFAT impacts immune-cell functions by regulating ECM remodeling.
ER -
TIDU, Federico, Marco DE ZUANI, Shyam Sushama JOSE, Kamila BENDICKOVA, Lukáš KUBALA, Frank CARUSO, Francesca CAVALIERI, Giancarlo FORTE and Jan FRIČ. NFAT signaling in human mesenchymal stromal cells affects extracellular matrix remodeling and antifungal immune responses. \textit{iSCIENCE}. CAMBRIDGE: CELL PRESS, 2021, vol.~24, No~6, p.~1-24. ISSN~2589-0042. Available from: https://dx.doi.org/10.1016/j.isci.2021.102683.
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