Indirect immune system modulation via paracrine secretome and cell-cell contact

Indirect immune system modulation via paracrine secretome and cell-cell contact is a multifaceted therapeutic mechanism primarily associated with Mesenchymal Stem/Stromal Cells (MSCs) and other cell-based therapies (Galipeau & Sensébé, 2018). Rather than acting through a single molecular target, this process involves the coordinated release of a 'secretome'—comprising cytokines (e.g., IL-10, TGF-β), chemokines, and extracellular vesicles—and direct physical interactions with immune cells via surface molecules like PD-L1 and HLA-G5 (Fan et al., 2020). These interactions collectively shift the immune system from a pro-inflammatory to an anti-inflammatory or regulatory state, inhibiting the activation of T-cells, B-cells, and Natural Killer cells while promoting the expansion of regulatory T-cells (Pittenger et al., 2019). This mechanism is central to the treatment of inflammatory and autoimmune conditions, such as Graft-versus-Host Disease (GvHD) and Crohn's disease, where systemic immune regulation is required. Because it encompasses a broad array of signaling pathways and physical interactions, it is classified as a therapeutic strategy or mechanism of action rather than a discrete molecular target.

Other names

Mesenchymal stem cell-mediated immunomodulationParacrine and juxtacrine immune regulationCell-mediated immunosuppressionMSC secretome-based therapy

Simultaneous secretion of anti-inflammatory soluble factors (paracrine) and direct surface protein binding (cell-cell contact) to suppress effector immune cells and induce immune tolerance.