REVIEW article

Front. Immunol.

Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1589853

Lactate and Lactylation: Emerging Roles in Autoimmune Diseases and Metabolic Reprogramming

Provisionally accepted
Wenjun  LiuWenjun Liu1Ruhui  YangRuhui Yang2Yuxin  ZhanYuxin Zhan2Xuanyu  YangXuanyu Yang2Haimin  ZengHaimin Zeng2Bofan  ChenBofan Chen2Jiahao  ZengJiahao Zeng2Tianheng  HuTianheng Hu2Jie  HuJie Hu3Qi  XiaoQi Xiao1Hangyu  LiHangyu Li1Xiang  ChenXiang Chen2*
  • 1Nanchang University, Nanchang, Jiangxi Province, China
  • 2Second Affiliated Hospital of Nanchang University, Nanchang, China
  • 3Ganzhou Municipal Hospital, Ganzhou, Jiangxi Province, China

The final, formatted version of the article will be published soon.

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 signalling 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.

Keywords: Lactate, lactylation, Autoimmune Diseases, metabolic reprogramming, epigenetics

Received: 08 Mar 2025; Accepted: 06 Jun 2025.

Copyright: © 2025 Liu, Yang, Zhan, Yang, Zeng, Chen, Zeng, Hu, Hu, Xiao, Li and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Xiang Chen, Second Affiliated Hospital of Nanchang University, Nanchang, China

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