Number of the records: 1
NFAT signaling in human mesenchymal stromal cells affects extracellular matrix remodeling and antifungal immune responses
- 1.
SYSNO ASEP 0554898 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title NFAT signaling in human mesenchymal stromal cells affects extracellular matrix remodeling and antifungal immune responses Author(s) Tidu, F. (CZ)
De Zuani, M. (CZ)
Jose, S. (CZ)
Bendíčková, K. (CZ)
Kubala, Lukáš (BFU-R) RID, ORCID
Caruso, F. (AU)
Cavalieri, F. (AU)
Forte, G. (CZ)
Frič, J. (CZ)Number of authors 9 Article number 102683 Source Title iScience. - : Cell Press
Roč. 24, č. 6 (2021)Number of pages 25 s. Publication form Online - E Language eng - English Country US - United States Keywords toll-like receptors ; beta-glucan recognition ; c-type lectin ; stem-cells ; hyaluronan degradation ; activation OECD category Biophysics Method of publishing Open access Institutional support BFU-R - RVO:68081707 UT WOS 000667301700118 EID SCOPUS 85109156613 DOI 10.1016/j.isci.2021.102683 Annotation 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. Workplace Institute of Biophysics Contact Jana Poláková, polakova@ibp.cz, Tel.: 541 517 244 Year of Publishing 2022 Electronic address https://www.sciencedirect.com/science/article/pii/S2589004221006519?via%3Dihub#!
Number of the records: 1