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Beyond soluble mediators, mast cell\u2010derived extracellular vesicles (MC\u2010EVs) are crucial for intercellular communication. MC\u2010EV heterogeneity, influenced by cellular activation and microenvironment, drives diverse biological roles. This review synthesizes current MC\u2010EV biology, cellular interactions, and translational potential in immunity, inflammation, and disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We systematically reviewed literature (2001\u20132024) from PubMed, Web of Science, and Scopus on MC\u2010EV biogenesis, cargo, and functional roles from in vitro, in vivo, and clinical studies, emphasizing recent advances across diverse disease context.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MC\u2010EVs exhibit profound heterogeneity, with distinct cargo profiles driven by cellular activation (e.g., inflammatory proteins\/miRNAs from activated MCs vs. homeostatic cargoes from resting MCs). These vesicles critically mediate intercellular communication, enhancing immune responses by promoting dendritic cell maturation, T lymphocyte activation, and IL\u20105 production in group 2 innate lymphoid cells. Their influence extends to epithelial cells, regulating epithelial\u2010to\u2010mesenchymal transition and disrupting barrier function context\u2010dependently. Pathologically, MC\u2010EVs exert dual roles in cancer, drive organ damage in mastocytosis, and modulate tissue microenvironments (e.g., neuroinflammation, bone marrow). This diverse functionality highlights their potential as diagnostic biomarkers and engineered therapeutic tools.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>MC\u2010EVs are critical, multifaceted mediators orchestrating communication between mast cells and diverse cell types, and mediate context\u2010specific immune modulation, remodeling, and disease progression. Deciphering cargo sorting, release and recipient uptake will enable MC\u2010EV\u2013based biomarkers and therapies for inflammatory, neoplastic, and hematopoietic conditions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/iid3.70452","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T07:11:02Z","timestamp":1776928262000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extracellular Vesicles: A Mailcoach From Mast Cell to Other Cell Species"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9470-032X","authenticated-orcid":false,"given":"Bingqi","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, The Eighth People's Hospital of Chengdu Geriatric Hospital of Chengdu Medical College Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yueshan","family":"Sun","sequence":"additional","affiliation":[{"name":"Medical Research Center, The Affiliated Hospital of Southwest Jiaotong University The Third People's Hospital of Chengdu Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0462-5158","authenticated-orcid":false,"given":"Tao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory The People's Hospital of Jianyang City Jianyang Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Runmin","family":"Long","sequence":"additional","affiliation":[{"name":"Medical Research Center, The Affiliated Hospital of Southwest Jiaotong University The Third People's Hospital of Chengdu Chengdu Sichuan 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