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Apoptotic T cells and their products play an important role in regulating inflammation and maintaining physiological immune homeostasis. Here it is shown that systemically infused T cell\u2010derived apoptotic extracellular vesicles (ApoEVs) can target mice irradiated intestines and alleviate radiation enteritis. Mechanistically, radiation elevates the synthesis of intestinal 2\u20323\u2032 cyclic GMP\u2010AMP (cGAMP) and activates cyclic GMP\u2010AMP synthase (cGAS)\u2010stimulator of interferon genes (STING) proinflammatory pathway. After systemic infusion of ApoEVs, the ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) enriches on the surface of ApoEVs hydrolyze extracellular cGAMP, resulting in inhibition of the cGAS\u2010STING pathway activated by irradiation. Furthermore, after ApoEVs are phagocytosed by phagocytes, ENPP1 on ApoEVs hydrolyzed intracellular cGAMP, which serves as an intracellular cGAMP hydrolyzation mode, thereby alleviating radiation enteritis. The findings shed light on the intracellular and extracellular hydrolysis capacity of ApoEVs and their role in inflammation regulation.<\/jats:p>","DOI":"10.1002\/advs.202401634","type":"journal-article","created":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T11:05:16Z","timestamp":1718708716000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["T Cell\u2010Derived Apoptotic Extracellular Vesicles Hydrolyze cGAMP to Alleviate Radiation Enteritis via Surface Enzyme ENPP1"],"prefix":"10.1002","volume":"11","author":[{"given":"Yang","family":"Zhou","sequence":"first","affiliation":[{"name":"College of Life Sciences Northwest University  Xi'an Shaanxi 710069 China"},{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi International Joint Research Center for Oral Diseases Center for Tissue Engineering School of 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