Decrease of NAD+ Inhibits the Apoptosis of OLP T Cells via Inducing Mitochondrial Fission

Purpose: Oral Lichen planus (OLP) is a chronic, immune-mediated inflammatory disease involving T cells. Mitochondrial fission plays a crucial role in T cell fate through structural remodeling. Nicotinamide adenine dinucleotide (NAD⁺) regulates mitochondrial remodeling and function. This study explored the role of NAD⁺ in modulating mitochondrial fission and Apoptosis in T cells under the OLP immune-inflammatory environment.

Patients and methods: T cells and plasma were isolated from peripheral blood. Mitochondrial morphology was characterized by transmission electron microscopy and Mito-Tracker staining. OLP plasma-exposed Jurkat T cells were infected with the Drp1 shRNA virus to investigate the role of mitochondrial fission in OLP T cell Apoptosis. OLP T cells and OLP plasma-exposed Jurkat T cells were treated with either β-nicotinamide mononucleotide (an NAD⁺ synthesis precursor) or FK866 (an NAD⁺ synthesis inhibitor) to assess the effect of NAD⁺ regulation on mitochondrial remodeling and T cell Apoptosis.

Results: OLP T cells exhibited fragmented mitochondria with elevated dynamin-related protein 1 (Drp1) and reduced mitofusin 2 (Mfn2) expression, accompanied by decreased Apoptosis. Drp1 knockdown in OLP plasma-exposed Jurkat T cells increased Apoptosis and reduced proliferation. NAD⁺ levels were reduced in both OLP T cells and OLP plasma-treated Jurkat T cells, leading to enhanced mitochondrial fission, decreased mitochondrial membrane potential (MMP) and respiration function, and reduced Apoptosis rate. β-nicotinamide mononucleotide supplementation restored NAD⁺ levels, suppressed mitochondrial fission, improved MMP, and promoted Apoptosis in these cells.

Conclusion: Reduced NAD⁺ levels in OLP T cells enhanced mitochondrial fission and contributed to decreased Apoptosis. NAD⁺ supplementation mitigated these effects, suggesting a potential therapeutic strategy for restoring T cell homeostasis in OLP.

T cells; mitochondria; nicotinamide adenine dinucleotide; oral lichen planus.