Biphasic role of L-TGF-β2 in modulating lamprey inflammation: Insights into vertebrate immune evolution

The regulation of inflammatory balance is central to immune homeostasis, with disruptions contributing to autoimmune diseases. As representatives of early vertebrates, lampreys offer a valuable model for investigating the evolutionary foundations of immune regulation. This study examines the dual role of L-TGF-β2 in modulating inflammation in lampreys, providing insights into the evolutionary origins of immune homeostasis mechanisms. Using lipopolysaccharide (LPS)-induced inflammation models, recombinant L-TGF-β2 was found to enhance leukocyte chemotaxis in quiescent states while inhibiting excessive migration during activation. Quantitative PCR revealed that L-TGF-β2 stimulates pro-inflammatory cytokine expression during early inflammatory phases and attenuates it during resolution. Tissue-specific expression patterns of TGF-β receptors indicated their potential role in mediating the distinct regulatory effects of L-TGF-β2 across diverse immune environments. These findings align with the biphasic functions of TGF-β observed in higher vertebrates, underscoring the evolutionary conservation of this signaling pathway. This research enhances understanding the functional versatility of TGF-β signaling and its pivotal role in vertebrate immune evolution, providing insights into ancient mechanisms of immune homeostasis and their modern implications for inflammatory disease research.