tetano
Editor, Senior Moderator
Cells
. 2026 Mar 26;15(7):592.
doi: 10.3390/cells15070592.
Mesenchymal Stromal Cells Respond to SARS-CoV-2 Peptides and Exhibit Altered T-Cell Regulatory Capacity
Sabrina Summer[SUP] 1 [/SUP], Hermann Maximilian Wolf[SUP] 2 [/SUP], Viktoria Weber[SUP] 3 [/SUP], Michael B Fischer[SUP] 1 4 [/SUP]
Affiliations
Background: MSCs possess strong immunoregulatory properties and play a central role in maintaining immune homeostasis by limiting inflammatory responses. Their function is highly plastic and influenced by environmental cues, including viral signals. How SARS-CoV-2-derived antigens affect MSC immunoregulation remains incompletely understood. This study aimed to investigate the impact of SARS-CoV-2 peptides on MSC-mediated immune modulation of T-cells.
Methods: MSCs were stimulated directly with SARS-CoV-2 spike protein S peptides or cocultured with SARS-CoV-2 peptide-activated T-cells. TLR4 surface expression and receptor downstream signaling were assessed to evaluate pathway activation. MSC immunoregulatory function was analyzed by measuring suppression of TNF-α and IFN-γ expression and induction of CD4[SUP]+[/SUP]FOXP3[SUP]+[/SUP] regulatory T-cells. TLR4 inhibition and lipopolysaccharide (LPS) stimulation were used to examine pathway specificity and interaction.
Results: SARS-CoV-2 peptides activated TLR4-associated signaling in MSCs, increasing TLR4 expression and NF-κB phosphorylation. Peptide-treated MSCs showed impaired suppression of pro-inflammatory cytokines and reduced induction of regulatory T-cells. TLR4 inhibition prevented these effects. LPS induced similar effects, while combining LPS and peptide stimulation partially restored physiological T-cell cytokine suppression.
Conclusions: SARS-CoV-2 peptides modulate MSC immunoregulatory function on T-cells via TLR4-dependent mechanisms.
Keywords: COVID-19; SARS-CoV-2 peptides; T-cells; immunoregulation; mesenchymal stromal cells.
. 2026 Mar 26;15(7):592.
doi: 10.3390/cells15070592.
Mesenchymal Stromal Cells Respond to SARS-CoV-2 Peptides and Exhibit Altered T-Cell Regulatory Capacity
Sabrina Summer[SUP] 1 [/SUP], Hermann Maximilian Wolf[SUP] 2 [/SUP], Viktoria Weber[SUP] 3 [/SUP], Michael B Fischer[SUP] 1 4 [/SUP]
Affiliations
- PMID: 41972683
- DOI: 10.3390/cells15070592
Background: MSCs possess strong immunoregulatory properties and play a central role in maintaining immune homeostasis by limiting inflammatory responses. Their function is highly plastic and influenced by environmental cues, including viral signals. How SARS-CoV-2-derived antigens affect MSC immunoregulation remains incompletely understood. This study aimed to investigate the impact of SARS-CoV-2 peptides on MSC-mediated immune modulation of T-cells.
Methods: MSCs were stimulated directly with SARS-CoV-2 spike protein S peptides or cocultured with SARS-CoV-2 peptide-activated T-cells. TLR4 surface expression and receptor downstream signaling were assessed to evaluate pathway activation. MSC immunoregulatory function was analyzed by measuring suppression of TNF-α and IFN-γ expression and induction of CD4[SUP]+[/SUP]FOXP3[SUP]+[/SUP] regulatory T-cells. TLR4 inhibition and lipopolysaccharide (LPS) stimulation were used to examine pathway specificity and interaction.
Results: SARS-CoV-2 peptides activated TLR4-associated signaling in MSCs, increasing TLR4 expression and NF-κB phosphorylation. Peptide-treated MSCs showed impaired suppression of pro-inflammatory cytokines and reduced induction of regulatory T-cells. TLR4 inhibition prevented these effects. LPS induced similar effects, while combining LPS and peptide stimulation partially restored physiological T-cell cytokine suppression.
Conclusions: SARS-CoV-2 peptides modulate MSC immunoregulatory function on T-cells via TLR4-dependent mechanisms.
Keywords: COVID-19; SARS-CoV-2 peptides; T-cells; immunoregulation; mesenchymal stromal cells.