Program Results

Introduction to the event

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by defect in autoreactive B cell clearance that lead to excessive autoantibody production and various complications, particularly kidney injury. Current therapeutic strategies primarily focus on systemic immunosuppression to reduce autoantibody production, but their effectiveness in reversing organ damage remains limited.

Previously, we demonstrated the potential of modulating local T cell responses within inflamed tissue microenvironments, showing that hypoxia and the subsequent elevation of HIF-1 regulate renal-infiltrating T cell function by reversing the BNIP3-mediated apoptotic pathway and reprogramming cellular metabolism to promote glycolysis. This year, our team published a study further demonstrating similar HIF-1–driven regulatory changes in skin-infiltrating T cells.

In our current project, we propose two novel strategies to suppress cytotoxic T cell–mediated tissue injury in lupus nephritis: (1) modulating the adaptive response of T cells to endoplasmic reticulum (ER) stress, and (2) disrupting the survival niche of stem-like precursor T cells to reduce their subsequent generation of cytotoxic T cells.