Fig. 3.

Lactate participates in inflammatory responses and regulates the functions of immune cells. The inflammatory processes involving inflammatory immune cells are highly dynamic. ECs are initially activated and express cell adhesion molecules, which facilitate the adherence of immune cells to the vascular wall, increase vascular permeability, and contribute to edema. Neutrophils are rapidly recruited to the site of infection for ROS generation and the formation of neutrophil extracellular traps. Macrophages are then polarized into M1-like macrophages, leading to a proinflammatory response. As lactate accumulates, the ‘lactate clock’ turns. Lactylation induces M1-like macrophages to polarize into M2-like macrophages through epigenetic mechanisms. T cells successively differentiate into CD4⁺ T cells and CD8⁺ T cells. Accumulated lactate inhibits the production of IL-4 and IL-17 in NKT cells and promotes the differentiation of CD4⁺ T cells into Th1, Th2 and Th17 cells. Subsequently, the transformation of cell energy metabolism to glycolysis promotes the differentiation of naive CD8⁺ T cells into effector CD8⁺ T cells, which secrete TNF-α and IFN-γ. Eventually, T cells transform into Treg cells and memory CD8⁺ T cells in the resolution of inflammation. Moreover, the accumulation of lactate, which is produced by various immune cells, induces EC migration and angiogenesis, thereby helping maintain inflammatory homeostasis.