Taurine Attenuates M1 Macrophage Polarization and IL-1β Production by Suppressing the JAK1/2-STAT1 Pathway via Metabolic Reprogramming

Dysregulated macrophage polarization is associated with various diseases, including sepsis, atherosclerosis, and fibrotic diseases. While taurine is known to exert immunomodulatory effects, its mechanism in regulating M1 macrophage polarization and interleukin-1β (IL-1β) production remains incompletely understood. This study aimed to elucidate the role of taurine in modulating macrophage immunometabolism and inflammatory signaling. Using thioglycolate-elicited peritoneal macrophages and macrophage cell lines, we assessed taurine's impact on lipopolysaccharide (LPS)/interferon-γ (IFN-γ)-induced M1 polarization through metabolomics and a range of molecular biology techniques. Pharmacological manipulation of the JAK1/2-STAT1 pathway and an LPS-induced murine sepsis model were used for mechanistic and therapeutic validation. Our results demonstrate that taurine significantly suppressed M1 polarization. Metabolomic profiling uniquely identified a marked increase in intracellular spermine as a key metabolic alteration induced by taurine. This increased spermine subsequently inhibited JAK1/2-STAT1 activation, leading to reduced IL-1β release. In mice, taurine alleviated systemic inflammation, reduced pathological damage in multiple organs, and decreased intestinal M1 macrophage infiltration. These findings establish a novel mechanism where taurine attenuates M1 polarization and IL-1β production through metabolically driven spermine accumulation and subsequent JAK1/2-STAT1 suppression, highlighting its therapeutic potential for inflammatory diseases.