The Evolving Roles of Macrophages in Organ Transplantation

Figure 2

Macrophage-targeted therapy for transplant tolerance. Mregs are generated from bone marrow precursors in rodents or from monocytes in humans. Both the adoptive transfer of Mregs and the expansion of Mregs with neutrophil-derived CSF1 in vivo inhibit the anti-donor T-cell response. Alternatively, strategies that prevent the accumulation of macrophages within allografts, including depletion of macrophages, inhibition of macrophage migration, and blockade of monocyte recruitment, also promote graft survival and contribute to graft acceptance. Strategies suppressing the activation of macrophages with detrimental functions involved in alloimmunity might be an effective therapy, such as inhibiting M2 polarization with the P2x7R antagonist oATP. Moreover, either neutralization of the Fcγ receptor or treatment with several immunosuppressive drugs (glucocorticoids, rapamycin inhibitors, and mycophenolate mofetil) exerts suppressive effects on proinflammatory macrophages and prolongs graft survival.