Preclinical (mouse + in vitro) · PMID 41929248
NAD+ deficiency from tacrolimus-suppressed IDO1 promotes M1 macrophage polarization and kidney injury — VialBase Research
Tacrolimus suppresses IDO1, blocking tryptophan-to-kynurenine conversion
Last updated · 2026 · Ye, Zhang, Guo, Zhou, et al. · Front Immunol
Key findings
- Tacrolimus suppresses IDO1, blocking tryptophan-to-kynurenine conversion
- Impaired de novo NAD+ synthesis leads to NAD+ deficiency
- NAD+ deficiency enhances glycolysis and impairs fatty acid beta-oxidation
- Drives M1 macrophage polarization and kidney injury
- Exogenous kynurenine or PPARalpha activation reverses damage
Tacrolimus-Induced NAD+ Deficiency Causes Kidney Injury (PMID: 41929248)
Study Design
- Mouse model of tacrolimus-induced kidney injury
- In vitro macrophage studies
- Metabolomic analysis (glycolysis, fatty acid oxidation, acylcarnitines)
Key Results
- Tacrolimus —> suppressed IDO1 —> blocked Trp-to-KYN —> impaired de novo NAD+ synthesis
- NAD+ deficiency —> enhanced glycolysis + impaired beta-oxidation —> accumulation of fatty acids/acylcarnitines
- Metabolic shift promoted M1 macrophage polarization —> kidney injury
- Rescue: exogenous kynurenine supplementation OR PPARalpha activation
Mechanism Insight
Demonstrates that NAD+ deficiency is not just about aging — it can be iatrogenically induced (by immunosuppressants like tacrolimus) with specific organ consequences. The metabolic reprogramming cascade (NAD+ depletion —> glycolysis shift —> M1 polarization) is a general mechanism applicable to many inflammatory conditions.
Clinical Relevance
Important for transplant patients on tacrolimus: NAD+ supplementation could be protective against nephrotoxicity. Also provides a mechanistic link between NAD+ status and inflammatory polarization of macrophages.
See Also
- Parent compound: NAD+