Work

Tim-3/Galectin-9 Signaling Alleviates Severe Acute Pancreatitis and Regulates Polarization of Peritoneal Macrophages

Year: 2025

Type: article

Abstract: Severe acute pancreatitis (SAP) is a prevalent gastrointestinal disorder characterized by both local and systemic inflammatory responses. Peritoneal macrophages (PMOs) play a crucial role in propagating inflammation, and promoting their polarization toward the M2 phenotype can mitigate this response. T-cell immunoglobulin and mucin domain 3 (Tim-3) and Galectin-9 (Gal-9) are recognized as immune regulatory molecules. However their involvement in macrophage polarization during SAP remains unexplored. Administration of Tim-3 mAb and α-lactose in vivo reduced the expression of Tim-3 and Gal-9 on PMOs. This intervention resulted in increased expression of IL-6 and TNF-α, decreased levels of IL-10 and CD206, promoting PMOs M1 polarization. Consequently, the enhanced release of pro-inflammatory mediators further exacerbated pancreatic injury. Additionally, the expression levels of phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) were diminished. In vitro experiments revealed that downregulation of Tim-3 and Gal-9 resulted in enhanced expression of IL-6 and TNF-α, decreased levels of IL-10 and CD206, and diminished phosphorylation of JAK2 and STAT3. Conversely, upregulation of Gal-9 yielded opposing effects. When JAK2/STAT3 signaling pathway inhibitors were applied to the Gal-9 upregulation group, IL-10 and CD206 expression were inhibited, while IL-6 and TNF-α levels increased. Our findings demonstrate that Tim-3/Gal-9 signaling facilitates M2 polarization of PMOs, at least partially through modulation of JAK2/STAT3 pathway. This modulation alleviates the early inflammatory response, offering a potential therapeutic strategy for SAP management.

Source: Bratislavské lekárske listy/Bratislava medical journal

DOI: 10.1007/s44411-025-00365-5