瓜氨酸、乳酸和睾酮如何影响重症肌无力？2025免疫代谢机制详解

Regarding the other fitness-related metabolites explored in this study, citrulline is a non-essential amino acid that plays a crucial role in the urea cycle and can participate in nitric oxide production via the arginine-citrulline cycle, thereby regulating vascular function and immune responses. Studies have shown that CD8+ T cells can eliminate toxic ammonia generated through metabolism via this cycle, ensuring their survival and function (DOI: 10.1038/s41590-022-01365-1). It can be inferred that citrulline has a direct metabolic support role in T cell immunity, thus providing protection against LOMG. Citrulline is significantly negatively correlated with LOMG risk, but this finding is based on only three SNPs, making the results highly unstable and necessitating further validation with larger sample sizes. Lactate is not only a metabolic product of anaerobic glycolysis but also a hub for immunometabolism and epigenetic programming in trained immunity. Specifically, immune cells preferentially use lactate as a substrate for the tricarboxylic acid (TCA) cycle after training, and lactate can modulate chromatin accessibility and immune gene expression through histone lactylation, thereby enhancing innate immune function (DOI: 10.1038/s41467-025-58563-2). However, in the context of autoimmune diseases, hyperactive innate immune cells may exacerbate immune attacks against acetylcholine receptors, thus increasing the risk of MG, which is consistent with our findings. However, due to insufficient data on MG, we were unable to further confirm the causal relationship through reverse experiments. Additionally, testosterone, an important substance in fitness, can regulate muscle synthesis and immune function through exogenous supplementation or endogenously induced by exercise, thereby influencing T cell differentiation and susceptibility to autoimmunity. This study shows a negative correlation between testosterone and MG risk, but the weighted median method did not reach statistical significance, indicating poor reliability.