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Updated: Mar 6, 2026
High-Efficiency Generation of Antigen-Specific Primary Mouse Cytotoxic T Cells for Functional Testing in an Autoimmune Diabetes Model
Published on: August 16, 2019
Nanoassembly-mediated immunometabolic reprogramming of CD4+ T cells suppresses β-cell autoimmunity in type 1 diabetes
Xixi Nan1, Shuotong Zhang1, Xinyue Chu1
1Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China.
The pathogenesis of type 1 diabetes mellitus (T1DM), known as autoimmune diabetes, is thought to be mediated by T cell-driven destruction of β cells, with the hyperactivation of CD4+ T cells playing a central role by triggering increased T helper (Th)1 and Th17 differentiation and impaired regulatory T (Treg) cell function. Herein, we constructed a nanoassembly (aNAJPH) capable of regulating immunometabolic reprogramming of activated CD4+ T cells, thereby suppressing β-cell autoimmunity in T1DM. The anti-CD154-F(ab')2 fragments on the surface of aNAJPH blocked the essential secondary costimulatory signal required for the pathogenic response, while the encapsulated L-type amino acid transporter 1 inhibitor suppressed the hyperactive metabolic pathways in activated CD4+ T cells. This synergistic mechanism achieved a specific reduction in the frequency of pathogenic CD4+ T cells and restoration of immune homeostasis by redirecting their differentiation away from pro-inflammatory Th1/Th17 lineages and toward protective Treg lineage. Through this effect, it ultimately reduced CD4+ T cell infiltration into pancreatic islets, preserved islet architecture, maintained blood glucose homeostasis, and lowered systemic inflammatory cytokine levels. This work presents a synergistic immunometabolic targeting strategy to restore immune homeostasis and suppress β-cell autoimmunity, offering a precision framework for treating a broader range of autoimmune diseases.
The pathogenesis of type 1 diabetes mellitus (T1DM), known as autoimmune diabetes, is thought to be mediated by T cell-driven destruction of β cells, with the hyperactivation of CD4+ T cells playing a central role by triggering increased T helper (Th)1 and Th17 differentiation and impaired regulatory T (Treg) cell function. Herein, we constructed a nanoassembly (aNAJPH) capable of regulating immunometabolic reprogramming of activated CD4+ T cells, thereby suppressing β-cell autoimmunity in T1DM. The anti-CD154-F(ab')2 fragments on the surface of aNAJPH blocked the essential secondary costimulatory signal required for the pathogenic response, while the encapsulated L-type amino acid transporter 1 inhibitor suppressed the hyperactive metabolic pathways in activated CD4+ T cells. This synergistic mechanism achieved a specific reduction in the frequency of pathogenic CD4+ T cells and restoration of immune homeostasis by redirecting their differentiation away from pro-inflammatory Th1/Th17 lineages and toward protective Treg lineage. Through this effect, it ultimately reduced CD4+ T cell infiltration into pancreatic islets, preserved islet architecture, maintained blood glucose homeostasis, and lowered systemic inflammatory cytokine levels. This work presents a synergistic immunometabolic targeting strategy to restore immune homeostasis and suppress β-cell autoimmunity, offering a precision framework for treating a broader range of autoimmune diseases.
