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| Status |
Public on Jun 14, 2021 |
| Title |
NFAT signalling in human mesenchymal stromal cells affects extracellular matrix metabolism and anti-fungal immune responses |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Mesenchymal stromal cells (MSCs) combined with calcineurin-NFAT (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 GvHD patients, is unknown. We report that MSCs phagocytose the fungal component zymosan, resulting in phosphorylation of Syk kinase, increase in cytosolic calcium levels and ultimately, 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-κB pathway. When co-culturing 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-κB directly controls inflammatory cytokine expression, NFAT impacts immune-cell functions by regulating ECM remodelling.
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| Overall design |
mRNA transcriptome of human adipose derived mesenchymal stromal cells (AT-MSCs) treated with zymosan in presence or absence of CN-NFAT inhibitor FK506
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| Web link |
https://0-doi-org.brum.beds.ac.uk/10.1016/j.isci.2021.102683
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| Contributor(s) |
Tidu F, De Zuani M, Jose SS, Bendickova K, Kubala L, Caruso F, Cavalieri F, Forte G, Fric J |
| Citation(s) |
34195564 |
| Submission date |
Sep 15, 2020 |
| Last update date |
Sep 13, 2021 |
| Contact name |
Marco De Zuani |
| Organization name |
FNUSA - ICRC
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| Department |
CTM
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| Lab |
CMI
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| Street address |
Pekarska, 53
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| City |
Brno |
| ZIP/Postal code |
65691 |
| Country |
Czech Republic |
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| Platforms (1) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA663579 |
| SRA |
SRP282462 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE157981_RAW.tar |
1.7 Mb |
(http)(custom) |
TAR (of CSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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