Adoptive Transfer of Immunomodulatory M2 Macrophages Prevents Type 1 Diabetes in NOD Mice

2012/06/30 by Roham Parsa, Pernilla Andresen, Alan Gillett +6 · 25 citations
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · Medicine · #Adoptive cell transfer #Autoimmunity #Biology #Cancer research #Diabetes and associated disorders #Diabetes mellitus #Endocrinology #Immune Cell Function and Interaction #Immune cells in cancer #Immune system #Immunology #Immunotherapy #In vitro #Inflammation #Macrophage #Medicine #NOD mice #Nod #Proinflammatory cytokine #T cell

paper · pdf · doi:10.2337/db11-1635

openalex publication_date 2012/06/30 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31

Abstract

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-β (TGF-β) to be optimal. M2r cells expressed programmed cell death 1 ligand-2, fragment crystallizable region γ receptor IIb, IL-10, and TGF-β, had a potent deactivating effect on proinflammatory lipopolysaccharide/interferon-γ-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 β-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.

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