Liu Wenjun, Yang Ruhui, Zhan Yuxin, Yang Xuanyu, Zeng Haimin, Chen Bofan, Zeng Jiahao, Hu Tianheng, Hu Jie, Xiao Qi, Shao Yinjin, Chen Xiang
Department of Rehabilitation Medicine, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
Queen Mary School, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Front Immunol. 2025 Jun 27;16:1589853. doi: 10.3389/fimmu.2025.1589853. eCollection 2025.
Autoimmune diseases are a set of conditions in which the immune system incorrectly identifies and attacks the body's own healthy tissue, severely compromising patient health. While current treatments can somewhat control disease progression, their long-term effectiveness remains limited, necessitating the development of more effective therapeutic approaches. Lactate and lactylation are critical links between metabolic reprogramming and epigenetics. As an emerging epigenetic modification, lactylation induced by lactate is closely associated with the onset of autoimmune diseases. Lactylation can be categorized into histone and nonhistone modifications, both of which play pivotal roles in cellular functions and pathophysiological processes through distinct regulatory mechanisms. Lactylation impacts immune cell function by regulating metabolic reprogramming and signaling pathways. In autoimmune diseases, immune cell metabolic reprogramming controls lactylation levels through metabolic byproducts, and lactylation, in turn, modulates the cellular metabolism by altering the transcription and structure of key enzymes. These interconnected processes collectively drive disease progression. To better understand the role of lactate and lactylation in the pathogenesis of autoimmune diseases, this review synthesizes the effects on specific immune cells, examining their dual effects on immune system function and their particular impacts on two common autoimmune diseases-rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). By combining the established role of lactate in immune metabolic reprogramming with the emerging understanding of the influence of lactate-induced lactylation on epigenetic regulation, this paper explores the relationship between lactylation and the progression of autoimmune diseases. This approach aims to enhance the understanding of the interplay between epigenetics and metabolism in autoimmune disease development, providing new perspectives for future therapeutic strategies. Studies collectively indicate that treatment can be improved through regulating key enzymes involved in lactylation, targeting lactate production pathways, integrating innovative approaches with current therapies, and adopting personalized treatment strategies.
自身免疫性疾病是一组免疫系统错误识别并攻击机体自身健康组织的病症，严重损害患者健康。虽然目前的治疗方法能在一定程度上控制疾病进展，但其长期有效性仍然有限，因此需要开发更有效的治疗方法。乳酸和乳酸化是代谢重编程与表观遗传学之间的关键联系。作为一种新兴的表观遗传修饰，由乳酸诱导的乳酸化与自身免疫性疾病的发病密切相关。乳酸化可分为组蛋白修饰和非组蛋白修饰，二者均通过不同的调控机制在细胞功能和病理生理过程中发挥关键作用。乳酸化通过调节代谢重编程和信号通路影响免疫细胞功能。在自身免疫性疾病中，免疫细胞代谢重编程通过代谢副产物控制乳酸化水平，而乳酸化反过来通过改变关键酶的转录和结构来调节细胞代谢。这些相互关联的过程共同推动疾病进展。为了更好地理解乳酸和乳酸化在自身免疫性疾病发病机制中的作用，本综述综合了其对特定免疫细胞的影响，考察了它们对免疫系统功能的双重作用以及对两种常见自身免疫性疾病——类风湿性关节炎（RA）和系统性红斑狼疮（SLE）的具体影响。通过将乳酸在免疫代谢重编程中的既定作用与对乳酸诱导的乳酸化对表观遗传调控影响的新认识相结合，本文探讨了乳酸化与自身免疫性疾病进展之间的关系。这种方法旨在增进对自身免疫性疾病发展过程中表观遗传学与代谢之间相互作用的理解，为未来的治疗策略提供新的视角。研究共同表明，可通过调节参与乳酸化的关键酶、靶向乳酸产生途径、将创新方法与现有疗法相结合以及采用个性化治疗策略来改善治疗效果。
