Immunomodulation of mesenchymal stromal cells on regulatory T cells and its possible mechanism

• We confirm that MSCs can augment immunosuppressive capacity of Tregs.
• MSCs stimulate the PD-1 expression and IL-10/TGF-β1 releases in the cocultures.
• PD-1/B7-H1 signal and IL-10 may be involved in the inhibition of MSC-exposed Tregs.
• IL-10 partially contributes to the upregulation of PD-1 on MSC-exposed Tregs.
• IL-10 and TGF-β1 are independent of PD-1/B7-H1 interplay in MSC-Treg cocultures.

Mesenchymal stromal cells (MSCs) and regulatory T cells (Tregs) have both garnered abundant interests from immunologists worldwide, as both MSCs and Tregs can be considered immunosuppressive in their own right. But a little attention has been paid to the impacts of MSCs on Tregs. To clarify the effects of MSCs on Tregs, we performed the coculture systems within MSCs and Tregs. We confirmed that MSC-exposed Tregs are capable of more immunosuppressive than Tregs without coculturing with MSCs. And this augmenting suppressive capacity was accompanied with an upregulation of programmed cell death 1 receptor (PD-1) on Tregs. Importantly, we found that cell viability of Tregs was excluded from the influences of MSCs. Finally, we showed that PD-1/B7-H1 interactions and IL-10 might be responsible for the enhanced suppressive capability of MSC-exposed Tregs. Further analysis revealed that PD-1/B7-H1 interactions were not responsible for the productions of IL-10 and TGF-β1 in the MSC-Treg coculture systems; in contrast, IL-10 rather than TGF-β1 played a role in the upregualtion of PD-1. Furthermore, this is the first explorative study to evaluate the immunomodulation of MSCs on the suppressive capacity of Tregs in MSC–Treg in vitro coculture setting.