| First Author | Parsa R | Year | 2012 |
| Journal | Diabetes | Volume | 61 |
| Issue | 11 | Pages | 2881-92 |
| PubMed ID | 22745325 | Mgi Jnum | J:208522 |
| Mgi Id | MGI:5563641 | Doi | 10.2337/db11-1635 |
| Citation | Parsa R, et al. (2012) Adoptive transfer of immunomodulatory M2 macrophages prevents type 1 diabetes in NOD mice. Diabetes 61(11):2881-92 |
| abstractText | Macrophages are multifunctional immune cells that may either drive or modulate disease pathogenesis depending on their activation phenotype. Autoimmune type 1 diabetes (T1D) is a chronic proinflammatory condition characterized by unresolved destruction of pancreatic islets. Adoptive cell transfer of macrophages with immunosuppressive properties represents a novel immunotherapy for treatment of such chronic autoimmune diseases. We used a panel of cytokines and other stimuli to discern the most effective regimen for in vitro induction of immunosuppressive macrophages (M2r) and determined interleukin (IL)-4/IL-10/transforming growth factor-beta (TGF-beta) to be optimal. M2r cells expressed programmed cell death 1 ligand-2, fragment crystallizable region gamma receptor IIb, IL-10, and TGF-beta, had a potent deactivating effect on proinflammatory lipopolysaccharide/interferon-gamma-stimulated macrophages, and significantly suppressed T-cell proliferation. Clinical therapeutic efficacy was assessed after adoptive transfer in NOD T1D mice, and after a single transfer of M2r macrophages, >80% of treated NOD mice were protected against T1D for at least 3 months, even when transfer was conducted just prior to clinical onset. Fluorescent imaging analyses revealed that adoptively transferred M2r macrophages specifically homed to the inflamed pancreas, promoting beta-cell survival. We suggest that M2r macrophage therapy represents a novel intervention that stops ongoing autoimmune T1D and may have relevance in a clinical setting. |
