Pålsson-McDermott Eva M, O'Neill Luke A J
School of Biochemistry and Immunology, Trinity Biomedical Science Institute, Trinity College Dublin, Dublin 2, Ireland.
School of Biochemistry and Immunology, Trinity Biomedical Science Institute, Trinity College Dublin, Dublin 2, Ireland.
Cell Metab. 2025 May 6;37(5):1049-1059. doi: 10.1016/j.cmet.2025.03.004. Epub 2025 Mar 31.
The reprogramming of metabolic pathways and processes in immune cells has emerged as an important aspect of the immune response. Metabolic intermediates accumulate as a result of metabolic adaptations and mediate functions outside of metabolism in the regulation of immunity and inflammation. In macrophages, there has been a major focus on 3 metabolites linked to the Krebs cycle, itaconate, succinate, and fumarate, which have been shown to regulate multiple processes. Here, we discuss recent progress on these 3 metabolites with regard to their effect on macrophages in host defense and inflammatory diseases. We also consider the therapeutic opportunities presented from the mimicry of these metabolites or by targeting the enzymes that make or metabolize them in order to leverage the body's own anti-inflammatory response.
免疫细胞中代谢途径和过程的重编程已成为免疫反应的一个重要方面。代谢适应导致代谢中间产物积累，并在免疫和炎症调节中介导代谢之外的功能。在巨噬细胞中，主要关注与三羧酸循环相关的3种代谢产物——衣康酸、琥珀酸和富马酸，它们已被证明可调节多个过程。在此，我们讨论这3种代谢产物在宿主防御和炎症性疾病中对巨噬细胞影响的最新进展。我们还考虑了通过模拟这些代谢产物或靶向生成或代谢它们的酶所带来的治疗机会，以便利用机体自身的抗炎反应。
