NFAT signaling in human mesenchymal stromal cells affects
extracellular matrix remodeling and antifungal immune responses

J 2021

NFAT signaling in human mesenchymal stromal cells affects extracellular matrix remodeling and antifungal immune responses

TIDU, Federico, Marco DE ZUANI, Shyam Sushama JOSE, Kamila BENDICKOVA, Lukáš KUBALA et. al.

Basic information

Original name

NFAT signaling in human mesenchymal stromal cells affects extracellular matrix remodeling and antifungal immune responses

Authors

TIDU, Federico (380 Italy, belonging to the institution), Marco DE ZUANI, Shyam Sushama JOSE (203 Czech Republic), Kamila BENDICKOVA (203 Czech Republic), Lukáš KUBALA (203 Czech Republic), Frank CARUSO, Francesca CAVALIERI, Giancarlo FORTE (380 Italy) and Jan FRIČ (203 Czech Republic, guarantor)

Edition

iSCIENCE, CAMBRIDGE, CELL PRESS, 2021, 2589-0042

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10700 1.7 Other natural sciences

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 6.107

RIV identification code

RIV/00216224:14110/21:00122134

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/j.isci.2021.102683

UT WoS

000667301700118

Keywords in English

NFAT signaling; human mesenchymal stromal cells

Abstract

V originále

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.

Links

LM2015091, research and development project

Name: Národní centrum lékařské genomiky (Acronym: NCLG)

Investor: Ministry of Education, Youth and Sports of the CR

Citovat

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. 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.

@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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