Fig. 1

PD-L1 mediated immunomodulatory and therapeutic potential of mesenchymal stromal/stem cells (MSCs). PD-L1 expressed by MSCs can interact with PD1 on the surface of T cells in three mechanisms. In the first option, PD-L1 is transferred to the cell plasma membrane and, in this way, inhibits the functions of T cells through direct cell-to-cell interaction. In the second mechanism, PD-L1 is secreted into the extracellular environment. For this reason, MSCs-derived supernatant can induce PD-L1-mediated immunomodulatory functions in co-culture with T cells or PBMCs. In the third method, MSCs affect the response of T cells by transferring PD-L1 to extracellular vesicles (EVs) such as exosomes. The interaction between PD-1 and PD-L1 leads to the creation of signaling cascades in T cells, which inhibits their proliferation and differentiation into inflammatory populations, including Th1, Th2, and Th17, as well as the production of inflammatory cytokines. It has also been found that this interaction also inhibits the function of TCD8 + cells. However, this interaction increases the differentiation of T cells towards regulatory T cells. In addition, it has been shown that signal transmission from PD-1 leads to positive feedback to PD-L1⁺ MSCs and enhances their immunomodulatory functions. It has also been shown that the use of inflammatory environments and pretreatment of MSCs with TLR ligands, including poly I:C, can lead to an increase in the immunomodulatory potential of MSCs by increasing the expression and production of PD-L1. This is while the use of anti-PD-L1 antibodies and siRNA inhibiting its expression and translation can reduce the immunomodulatory potential of MSCs. Therefore, the expression of PD-L1 plays an essential role in the immunomodulatory potential of MSCs, which leads to an increase in its therapeutic potential in autoimmune colitis and psoriasis animal models