Islet transplantation modulates macrophage to induce immune tolerance and angiogenesis of islet tissue in type I diabetes mice model.

Objective To investigate the dual mechanism of islet transplantation in T1D by regulating the immune tolerance of macrophages and inducing the neovascularization. Methods NC group, T1D model group and T1D model + islet group were constructed. Then, the abdominal aorta blood of abdominal aorta and islet tissue were collected. ELISA was performed to detect the level of IL-1Rα, IL-1α, IL-1β, CXCL2, MCP1, TNF-α and IL-10. Flow cytometry was used to measure the content of M1 and M2 macrophages. HE staining indicated the pathological characteristics of islet. IHC and WB were applied to determine the protein levels of IGF1R, FGFR2 or VEGFA as well as IGF1R, GRB2, EGFR, PTPN1, JAK2, STAT3, Caspase-1, Bcl2 respectively. Results Islet transplantation in T1D stimulated the expression of IL-1Rα, IL-1α, IL-1β, CXCL2, MCP1, TNF-α and IL-10 in abdominal aorta blood, changed the content of MHCIICD206M1 and MHCIICD206M2 macrophages, reduced the pathological features and the infiltration of immunocytes, promoted the expression of IGF1R, FGFR2 and VEGFA, eliminated cell apoptosis and induced the neovascularization in islet grafts. Conclusions Islet transplantation is an effective strategy for the treatment of T1D. It can increase the content of M2 macrophages whose immune tolerance can elevate the survival of islet grafts, reduce the inflammatory responses mediated by macrophages, promote the neovascularization and eliminate the cell apoptosis of islet grafts.