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Engineered PD-L1-Expressing Platelets Reverse New-Onset Type 1 Diabetes.

Xudong Zhang^1,2, Yang Kang^1,2, Jinqiang Wang^1,2

¹Department of Bioengineering, University of California, Los Angeles, CA, 90095, USA.

Advanced Materials (Deerfield Beach, Fla.)

|May 26, 2020

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Engineered platelets overexpressing PD-L1 suppress autoimmune T cells in the pancreas. This approach rescues insulin-producing beta-cells, reverses diabetes, and restores immune tolerance in a mouse model of Type 1 diabetes.

Area of Science:

Immunology
Endocrinology
Cell Biology

Background:

Type 1 diabetes (T1D) pathogenesis involves autoimmune destruction of insulin-producing beta-cells by T cells.
The programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) pathway is crucial for regulating T cell activity and preventing autoimmunity.
Targeting T cell-mediated destruction of beta-cells is a key strategy for T1D treatment.

Purpose of the Study:

To investigate the therapeutic potential of genetically engineered platelets overexpressing PD-L1 (PD-L1 platelets) for treating new-onset T1D.
To determine if PD-L1 platelets can suppress autoreactive T cells in the pancreas and protect beta-cells.
To evaluate the impact of PD-L1 platelets on regulatory T cells (Tregs) and immune tolerance in a T1D model.

Main Methods:

Keywords:

drug delivery immune tolerance platelets programmed death-ligand 1 (PD-L1)type 1 diabetes (T1D)

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Genetic engineering of megakaryocyte progenitor cells to overexpress PD-L1.
Administration of PD-L1-overexpressing platelets to newly hyperglycemic non-obese diabetic (NOD) mice.
Assessment of T cell activity, beta-cell destruction, Treg populations, and glycemic control in treated mice.

Main Results:

PD-L1 platelets accumulated in the inflamed pancreas of NOD mice.
Treatment with PD-L1 platelets suppressed the activity of autoreactive pancreatic T cells.
PD-L1 platelets protected insulin-producing beta-cells from autoimmune destruction, leading to normoglycemia and diabetes reversal.
PD-L1 platelet therapy increased the percentage of regulatory T cells (Tregs) and promoted immune tolerance.

Conclusions:

Genetically engineered PD-L1 platelets represent a novel cell-based therapy for Type 1 diabetes.
PD-L1 platelets effectively rescue beta-cells by modulating the immune response in the pancreas.
This approach holds promise for maintaining normoglycemia and reversing diabetes in new-onset T1D.