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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023736%3A_____%2F21%3A00013257" target="_blank" >RIV/00023736:_____/21:00013257 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68081707:_____/21:00554898 RIV/00159816:_____/21:00075079 RIV/00216224:14110/21:00122134

Výsledek na webu

<a href="https://doi.org/10.1016/j.isci.2021.102683" target="_blank" >https://doi.org/10.1016/j.isci.2021.102683</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.isci.2021.102683" target="_blank" >10.1016/j.isci.2021.102683</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30205 - Hematology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

iScience

ISSN

2589-0042

e-ISSN

—

Svazek periodika

24

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

24

Strana od-do

"art. no. 102683"

Kód UT WoS článku

000667301700118

EID výsledku v databázi Scopus

2-s2.0-85109156613