英国伯明翰大学Claudio Mauro团队发现了慢性炎症部位的乳酸积累，通过诱导CD4⁺T细胞的代谢重组来促进疾病的发生。相关论文在线发表在2019年11月7日出版的《细胞—代谢》上。

研究评估了在慢性炎症的情况下免疫细胞对乳酸的应答。报告称，乳酸在发炎组织中的积累有助于人CD4⁺T细胞中乳酸转运蛋白SLC5A12的上调。SLC5A12介导的CD4⁺T细胞对乳酸的摄取可诱导其效应表型的重塑，从而通过核PKM2/STAT3导致IL17产生增加，并增强脂肪酸合成。由于糖酵解减少和脂肪酸合成增加，它也会导致CD4⁺T细胞滞留在炎症组织中。此外，抗体介导的SLC5A12阻断，可改善小鼠关节炎模型中的疾病严重程度。最后，他们提出乳酸/SLC5A12诱导的代谢重编程，是类风湿关节炎患者的淋巴滑膜炎的独特特征，也是慢性炎症性疾病的潜在治疗靶标。

据了解，乳酸在组织微环境中的积累，是炎症性疾病和癌症的特征。

附：英文原文

Title: Lactate Buildup at the Site of Chronic Inflammation Promotes Disease by Inducing CD4+ T Cell Metabolic Rewiring

Author: Valentina Pucino, Michelangelo Certo, Vinay Bulusu, Danilo Cucchi, Katriona Goldmann, Elena Pontarini, Robert Haas, Joanne Smith, Sarah E. Headland, Kevin Blighe, Massimiliano Ruscica, Frances Humby, Myles J. Lewis, Jurre J. Kamphorst, Michele Bombardieri, Costantino Pitzalis, Claudio Mauro

Issue&Volume: November 07, 2019

Abstract: Accumulation of lactate in the tissue microenvironment is a feature of both inflammatory disease and cancer. Here, we assess the response of immune cells to lactate in the context of chronic inflammation. We report that lactate accumulation in the inflamed tissue contributes to the upregulation of the lactate transporter SLC5A12 by human CD4+ T cells. SLC5A12-mediated lactate uptake into CD4+ T cells induces a reshaping of their effector phenotype, resulting in increased IL17 production via nuclear PKM2/STAT3 and enhanced fatty acid synthesis. It also leads to CD4+ T cell retention in the inflamed tissue as a consequence of reduced glycolysis and enhanced fatty acid synthesis. Furthermore, antibody-mediated blockade of SLC5A12 ameliorates the disease severity in a murine model of arthritis. Finally, we propose that lactate/SLC5A12-induced metabolic reprogramming is a distinctive feature of lymphoid synovitis in rheumatoid arthritis patients and a potential therapeutic target in chronic inflammatory disorders.

DOI: 10.1016/j.cmet.2019.10.004

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30559-5