Mesenchymal Stem Cell–Regulatory T cell interface (MSC–Treg interface)

The Mesenchymal Stem Cell–Regulatory T cell (MSC–Treg) interface is a complex multicellular signaling environment rather than a discrete molecular target. It functions as a regulatory hub where Mesenchymal Stem Cells (MSCs) modulate the adaptive immune system by promoting the polarization of naive T cells into immunosuppressive Regulatory T cells (Tregs) (Negi & Griffin, 2020). This process is mediated by a combination of secreted factors, including Indoleamine 2,3-dioxygenase (IDO), Prostaglandin E2 (PGE2), and Transforming Growth Factor-beta 1 (TGF-β1), alongside direct membrane-bound interactions like PD-L1/PD-1 and Notch signaling (Melief et al., 2013; Luz-Crawford et al., 2013). In therapeutic contexts, such as the treatment of Graft-versus-Host Disease (GvHD) and Crohn's disease, MSC-based products like Remestemcel-L leverage this interface to suppress pathological inflammation (Kuzmina et al., 2023). However, the complexity of this interaction presents challenges, including the potential for MSCs to switch to a pro-inflammatory phenotype under certain cytokine environments. Consequently, the MSC–Treg interface is a primary area of study for enhancing the precision and predictability of cell-based immunotherapies.

Other names

MSC-Treg axisMSC-Treg crosstalkMesenchymal Stromal Cell-Regulatory T cell interactionMSC-mediated Treg induction

Mesenchymal Stem Cells (MSCs) promote the induction, expansion, and functional stability of Regulatory T cells (Tregs) through the secretion of soluble immunomodulatory factors such as Indoleamine 2,3-dioxygenase (IDO), Prostaglandin E2 (PGE2), and Transforming Growth Factor-beta 1 (TGF-β1), as well as through direct cell-to-cell contact involving PD-L1/PD-1 and Notch signaling pathways (Negi & Griffin, 2020; Melief et al., 2013).