Soluble immunosuppressive checkpointome of mesenchymal stromal cells: Immunoregulatory mechanisms and a conceptual framework for potency assessment

Figure 3 Parallel signaling routes through which the four established members of the soluble checkpointome are induced and act. Each lane runs from the initiating signal at the top to the immunological outcome at the bottom, and the lanes converge only at the level of effector suppression. The interferon lane and the inflammation lane are licensed, the galectin-1 lane is constitutive, and the human leukocyte antigen-G5 lane requires cell contact. Terminal boxes denote the receptor engagement and its consequence. Pathway steps shown for each axis summarise the cited evidence; where a step is inferred from non-mesenchymal stromal cell (MSC) systems rather than demonstrated in MSCs it should be read as mechanistic context rather than established MSC biology, and the terminal outcomes do not exceed the effects reported in the cited studies. PD-L1: Programmed death ligand 1; IFN-γ: Interferon gamma; IFNGR: Interferon gamma receptor; JAK: Janus kinase; STAT1: Signal transducer and activator of transcription 1; IRF1: Interferon regulatory factor 1; PD-1: Programmed death-1; TNF-α: Tumor necrosis factor alpha; TLR: Toll-like receptor; TIM-3: T cell immunoglobulin and mucin domain-containing protein 3; NF-κB: Nuclear factor kappa B; NK: Natural killer; IL: Interleukin; HLA-G5: Human leukocyte antigen-G5; ILT: Immunoglobulin-like transcript; Treg: Regulatory T cell.