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Here, we found that the hepatic Treg proportion and \u03b2-catenin expression in hepatic macrophages were associated with acetaminophen- and d-galactosamine\/LPS\u2013induced acute liver injury. Interestingly, \u03b2-catenin was markedly upregulated only in infiltrating macrophages but not in resident Kupffer cells. Myeloid-specific \u03b2-catenin\u2013knockout mice showed an increased inflammatory cell infiltration and hepatocyte apoptosis. Moreover, myeloid \u03b2-catenin deficiency decreased the hepatic Treg proportion in the injured liver. Mechanistically, in vitro coculture experiments revealed that macrophage \u03b2-catenin modulated its exosome composition and influenced Treg differentiation. Using mass spectrometry\u2013based proteomics, we identified that macrophage \u03b2-catenin activation increased the level of exosomal alpha soluble NSF attachment protein (\u03b1-SNAP), which in turn promoted Treg differentiation. Overall, our findings demonstrated a molecular mechanism that macrophage \u03b2-catenin regulated the Treg proportion in the liver by enhancing the expression of exosomal \u03b1-SNAP, providing insights into the pathophysiology of acute liver injury.<\/jats:p>","DOI":"10.1172\/jci.insight.182515","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T12:00:43Z","timestamp":1732017643000},"source":"Crossref","is-referenced-by-count":3,"title":["\u03b2-Catenin disruption decreases macrophage exosomal \u03b1-SNAP and impedes Treg differentiation in acute liver injury"],"prefix":"10.1172","volume":"10","author":[{"given":"Ruobin","family":"Zong","sequence":"first","affiliation":[{"name":"Department of Physiology, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of 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