Targeting GLUT1 to Control Autoimmunity in Type 1 Diabetes

Type 1 Diabetes is an autoimmune disease characterized by immune-mediated destruction of pancreatic beta cells. Autoreactive T cells play a central role in this process and may persist over time within the memory T-cell compartment. Understanding the mechanisms that sustain autoreactive T-cell activation, survival, proliferation, and inflammatory function is therefore important for the development of more targeted immune-modulatory strategies.

Activated T cells undergo metabolic reprogramming to support their functional responses. In this context, glucose uptake and glycolytic metabolism are important components of T-cell activation. GLUT1 is a key glucose transporter involved in this metabolic adaptation and may contribute to the ability of autoreactive T cells to expand and maintain effector functions.

This study will use previously collected and biobanked peripheral blood mononuclear cell (PBMC) samples from individuals with Type 1 Diabetes. The PBMC samples will be retrieved in coded form, thawed, and infused into immunodeficient NOD scid gamma (NSG) mice to reconstitute a human immune system and generate humanized preclinical models. These models will be used to investigate the phenotype, activation state, metabolic profile, inflammatory function, and transcriptional features of human immune cells in relation to GLUT1 modulation. Experimental approaches include flow cytometry-based immunophenotyping, cytokine assessment, and transcriptomic analyses performed on human immune cells recovered from the humanized mice.

The study is observational and retrospective with respect to human participants. All human biological material and associated data were collected before the start of this study and are stored in coded or pseudonymized form. The study does not involve prospective enrollment of human participants, administration of an investigational product to human participants, additional biological sampling, clinical visits, or other study-specific procedures involving human participants.

The purpose of the study is to generate mechanistic and translational evidence on the role of GLUT1-dependent immune metabolism in Type 1 Diabetes-associated autoimmunity, using humanized preclinical models generated from biobanked PBMC samples. The study is intended to support the future development of targeted strategies aimed at modulating pathogenic autoreactive immune responses.

Inclusion criteria

• PBMC samples obtained from adult subjects aged 18 years or older at the time of sample collection.
• Documented diagnosis of Type 1 Diabetes.
• PBMC samples already collected and stored in the institutional Biobank of IRCCS Ospedale San Raffaele.
• PBMC samples obtained from subjects who had previously provided written informed consent for the collection, storage, and research use of biological material and associated data.

Exclusion criteria

• PBMC samples obtained from subjects younger than 18 years at the time of sample collection.
• Presence of relevant concomitant diseases or clinical conditions that, in the Investigator's judgment and based on available records, may interfere with the interpretation of immunological analyses or with the study objectives.
• Insufficient sample availability, inadequate sample quality, or missing essential sample-related information preventing use of the PBMC sample for the planned research activities.