Adoptive transfer of immunomodulatory M2 Macrophages prevents type 1 Diabetes in NOD Mice
2012 (English)In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 61, no 11, 2881-2892 p.Article in journal (Refereed) Published
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 IIlb, 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 3-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. Diabetes 61:2881-2892, 2012
Place, publisher, year, edition, pages
American diabetes Association , 2012. Vol. 61, no 11, 2881-2892 p.
Immunology in the medical area Basic Medicine
IdentifiersURN: urn:nbn:se:umu:diva-63774DOI: 10.2337/db11-1635ISI: 000312041600026OAI: oai:DiVA.org:umu-63774DiVA: diva2:587564