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Bioengineering Platelets Presenting PD-L1, Galectin-9 and BTLA to Ameliorate Type 1 Diabetes.
Yumeng Ma1,2, Fanqiang Meng1,2, Zhongda Lin1,2
1Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, Guangdong, 518107, P. R. China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|February 28, 2025
Summary
Interferon-gamma (IFN-γ) primed platelets effectively treat type 1 diabetes (T1D) in mice by inducing T cell exhaustion and promoting regulatory T cells, preserving beta-cell function and insulin production.
Area of Science:
- Immunology
- Endocrinology
- Cell Biology
Background:
- Type 1 diabetes (T1D) results from autoimmune destruction of pancreatic beta-cells, leading to insulin deficiency.
- Immunomodulation targeting autoreactive T cells is a key strategy for T1D treatment.
- Current T1D therapies aim to restore immune balance and protect beta-cells.
Purpose of the Study:
- To investigate the therapeutic potential of engineered platelets in a mouse model of T1D.
- To determine if IFN-γ-primed platelets can modulate immune responses and preserve beta-cell function.
- To explore the mechanisms by which IFN-γ platelets exert their immunomodulatory effects.
Main Methods:
- Megakaryocytes were primed with interferon-gamma (IFN-γ) to generate IFN-γ platelets expressing immunosuppressive ligands (PD-L1, PD-L2, BTLA, Gal-9).
- In vitro studies assessed the interaction of IFN-γ platelets with T cells, evaluating T cell exhaustion and apoptosis.
- Non-obese diabetic (NOD) mice with new-onset T1D were treated with IFN-γ platelets, and outcomes including beta-cell integrity, insulin production, and immune cell populations were analyzed.
Main Results:
- IFN-γ platelets induced T cell exhaustion and apoptosis in vitro through immune checkpoint interactions.
- In vivo, IFN-γ platelet treatment preserved beta-cell integrity and insulin production in NOD mice, preventing hyperglycemia.
- Treatment significantly reduced pancreatic infiltrating T cells, increased regulatory T cells (Tregs), and promoted M2 macrophage polarization.
Conclusions:
- IFN-γ platelets represent a novel cell-based therapy for T1D, effectively halting disease progression in a preclinical model.
- The therapeutic effects are mediated by inducing T cell exhaustion, promoting Treg expansion, and shifting macrophage phenotype towards an anti-inflammatory state.
- IFN-γ platelets hold promise for stimulating pancreatic angiogenesis and beta-cell proliferation, offering a potential avenue for T1D amelioration.
