Macrophage Tim-4 protects against deep vein thrombosis by binding CK2β to suppress inflammatory responses.

Background: Deep vein thrombosis (DVT) is a venous reflux disorder caused by dysregulated coagulation, with macrophage inflammatory responses being critical for its progression. T-cell immunoglobulin and mucin domain containing 4 (Tim-4) is known as a key regulator of macrophage function and inflammation. However, its involvement in DVT remains completely unclear. Methods: Tim-4 expression was comprehensively assessed in peripheral blood mononuclear cells from DVT patients and inferior vena cava-associated macrophages in both clinical specimens and murine DVT models using integrated approaches including single-cell RNA sequencing, immunofluorescence, flow cytometry, quantitative PCR, and Western blot. Macrophage-specific Results: Tim-4 was significantly downregulated in DVT-associated macrophages, correlating with elevated proinflammatory cytokine levels. Macrophage-specific Conclusions: Our findings demonstrate that macrophage Tim-4, regulated by lncRNF219-3:1/miR-93-5p axis, functions as a critical suppressor of DVT through hijacking and sequestering CK2β to dampen NF-κB mediated inflammation. The study unveils novel immunomodulatory mechanisms in DVT pathogenesis and highlights Tim-4 and its regulatory network as potential therapeutic targets for DVT in clinic.