Fig. 7: Schematic showing putative mechanism of hMSCs mediated immunosuppression in experimental model of Crohn’s disease.
In the early stage, live hMSC secretion of molecules like PGE2 is the dominant mechanism. PGE2 is released by hMSCs in the peritoneal cavity which diffuses through the fenestrated mesenteric lymphatic vessels to reach mLN, inhibit naïve T cell proliferation and educate SVF and mLN resident macrophages to anti-inflammatory phenotype with subsequent downregulation of proinflammatory cytokines, and enhance macrophages efferocytosis capacity. In the later phase, macrophages efferocytose apoptotic hMSCs, which leads to their proliferation and reprogramming to an anti-inflammatory phenotype that maintains and mediates the long-term effect.
