Inhibiting Inflammation with Myeloid Cell-Specific Nanobiologics Promotes Organ Transplant Acceptance.

ABSTRACT: Inducing graft acceptance without chronic immunosuppression remains an elusive goal in organ transplantation. Using an experimental transplantation mouse model, we demonstrate that local macrophage activation through dectin-1 and toll-like receptor 4 (TLR4) drives trained immunity-associated cytokine production during allograft rejection. We conducted nanoimmunotherapeutic studies and found that a short-term mTOR-specific high-density lipoprotein (HDL) nanobiologic treatment (mTORi-HDL) averted macrophage aerobic glycolysis and the epigenetic modifications underlying inflammatory cytokine production. The resulting regulatory macrophages prevented alloreactive CD8⁺ T cell-mediated immunity and promoted tolerogenic CD4⁺ regulatory T (Treg) cell expansion. To enhance the

SUBMITTER: Braza MS 

PROVIDER: S-EPMC6251711 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature