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.

Základní údaje

Originální název

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

Autoři

TIDU, Federico (380 Itálie, domácí), Marco DE ZUANI, Shyam Sushama JOSE (203 Česká republika), Kamila BENDICKOVA (203 Česká republika), Lukáš KUBALA (203 Česká republika), Frank CARUSO, Francesca CAVALIERI, Giancarlo FORTE (380 Itálie) a Jan FRIČ (203 Česká republika, garant)

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10700 1.7 Other natural sciences

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 6.107

Kód RIV

RIV/00216224:14110/21:00122134

Organizační jednotka

Lékařská fakulta

DOI

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

UT WoS

000667301700118

Klíčová slova anglicky

NFAT signaling; human mesenchymal stromal cells

Štítky

14110513, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 25. 3. 2022 09:14, Mgr. Tereza Miškechová

Anotace

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.

Návaznosti

LM2015091, projekt VaV

Název: Národní centrum lékařské genomiky (Akronym: NCLG)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Národní centrum lékařské genomiky

Citovat

TIDU, Federico, Marco DE ZUANI, Shyam Sushama JOSE, Kamila BENDICKOVA, Lukáš KUBALA, Frank CARUSO, Francesca CAVALIERI, Giancarlo FORTE a Jan FRIČ. NFAT signaling in human mesenchymal stromal cells affects extracellular matrix remodeling and antifungal immune responses. iSCIENCE. CAMBRIDGE: CELL PRESS, 2021, roč. 24, č. 6, s. 1-24. ISSN 2589-0042. Dostupné z: 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 a Jan FRIČ. NFAT signaling in human mesenchymal stromal cells affects extracellular matrix remodeling and antifungal immune responses. \textit{iSCIENCE}. CAMBRIDGE: CELL PRESS, 2021, roč.~24, č.~6, s.~1-24. ISSN~2589-0042. Dostupné z: https://dx.doi.org/10.1016/j.isci.2021.102683.

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