Canagliflozin impairs T cell effector function via metabolic suppression in autoimmunity

Area of Science:

• Immunology
• Metabolic pathways
• Drug repurposing

Background:

• Metabolic dysregulation contributes to T cell-mediated host damage in autoimmunity.
• Targeting immunometabolism is a promising therapeutic strategy for autoimmune disorders.
• The impact of SGLT2 inhibitors on human T cell function remains underexplored.

Purpose of the Study:

• To investigate the effects of the SGLT2 inhibitor canagliflozin on human T cell function.
• To explore the potential of canagliflozin as a therapeutic intervention for T cell-mediated autoimmunity.

Main Methods:

• Treatment of human T cells with canagliflozin.
• Assessment of T cell activation, proliferation, and effector functions.
• Analysis of T cell receptor signaling, ERK, mTORC1, and c-Myc activity.
• Evaluation of protein and solute carrier production.

Main Results:

• Canagliflozin treatment compromised T cell activation, proliferation, and effector functions.
• Canagliflozin inhibited T cell receptor signaling, reducing ERK, mTORC1, and c-Myc.
• Impaired c-Myc levels led to reduced metabolic protein and solute carrier production.
• Canagliflozin-treated T cells from autoimmune patients showed impaired effector function.

Conclusions:

• Canagliflozin negatively impacts human T cell function by disrupting key signaling pathways and metabolic processes.
• Repurposing canagliflozin offers a potential therapeutic strategy for T cell-mediated autoimmune diseases.