{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T06:13:52Z","timestamp":1788329632771,"version":"build-2803163510"},"reference-count":73,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI 118777"],"award-info":[{"award-number":["R01 AI 118777"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01AI132758"],"award-info":[{"award-number":["U01AI132758"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["T32 AI74490"],"award-info":[{"award-number":["T32 AI74490"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"American Society of Transplantation (AST) Research Network Fellowship Research Grant","award":["gVRC-22C1CA"],"award-info":[{"award-number":["gVRC-22C1CA"]}]},{"name":"NIH T32","award":["AI089443"],"award-info":[{"award-number":["AI089443"]}]},{"DOI":"10.13039\/100007921","name":"University of Pittsburgh","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007921","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH P30","award":["DK120531"],"award-info":[{"award-number":["DK120531"]}]},{"name":"University of Pittsburgh supports the Pittsburgh Liver Research Center"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hepatic ischemia-reperfusion (I\/R) injury triggers release of small extracellular vesicles (sEVs) that can function as systemic conveyors of inflammatory signals. While sEV-mediated immune cell modulation has been studied extensively in vitro, knowledge is based largely on sEVs derived from cultured cells, rather than injured tissues. Consequently, the immunological impact of liver I\/R-sEVs is poorly understood. Here, we combined in vitro and in vivo approaches with sEVs purified from mouse livers subjected to I\/R to define their influence on dendritic cells (DCs). In vitro, in contrast to sham-sEVs, I\/R-sEVs activated syngeneic bone marrow-derived DCs (BMDCs), inducing upregulation of costimulatory molecules and enhancing their capacity to stimulate naive allogeneic T-cells. In contrast, liver DCs (LDCs) were refractory to liver I\/R-sEV-mediated activation. This differential responsiveness may in part reflect greater I\/R-sEV internalization by BMDCs. To assess in vivo relevance, labeled sham or I\/R-sEVs were administered intravenously. Following systemic delivery, syngeneic I\/R-sEVs, but not sham-sEVs, accumulated in liver and spleen of otherwise naive mice exhibiting different patterns of uptake by immune cell populations. In the spleen, macrophages and B-cells were the principal I\/R-sEV-acquiring populations, whereas in the liver, sEV uptake was dominated by macrophages and neutrophils. Additionally, while splenic DCs showed increased expression of activation markers and T-cell stimulatory activity following exposure to I\/R-sEVs, LDCs were unresponsive. These findings identify liver-I\/R-sEVs as promotors of extra-hepatic DC maturation\/activation, whereas liver-resident DCs were refractory to I\/R-sEV stimulation. The findings have implications for regulation of inflammatory responses following liver I\/R injury.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag224","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T05:29:32Z","timestamp":1788326972000},"source":"Crossref","is-referenced-by-count":0,"title":["Differential responses of liver versus lymphoid tissue DC to small extracellular vesicles generated by hepatic ischemia-reperfusion injury"],"prefix":"10.1093","volume":"215","author":[{"given":"Cindy G","family":"Avalos-de Leon","sequence":"first","affiliation":[{"name":"Thomas E. Starzl Transplantation Institute, University of Pittsburgh , Pittsburgh, PA,","place":["United States"]},{"name":"Department of Surgery, University of Pittsburgh , Pittsburgh, PA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan F","family":"Zahorchak","sequence":"additional","affiliation":[{"name":"Thomas E. Starzl Transplantation Institute, University of Pittsburgh , Pittsburgh, PA,","place":["United States"]},{"name":"Department of Surgery, University of Pittsburgh , Pittsburgh, PA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suguru","family":"Mitsufuji","sequence":"additional","affiliation":[{"name":"Thomas E. Starzl Transplantation Institute, University of Pittsburgh , Pittsburgh, PA,","place":["United States"]},{"name":"Department of Surgery, University of Pittsburgh , Pittsburgh, PA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bala","family":"Ramaswami","sequence":"additional","affiliation":[{"name":"Thomas E. Starzl Transplantation Institute, University of Pittsburgh , Pittsburgh, PA,","place":["United States"]},{"name":"Department of Surgery, University of Pittsburgh , Pittsburgh, PA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamza O","family":"Yazdani","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Pittsburgh , Pittsburgh, PA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6723-4299","authenticated-orcid":false,"given":"Yannis","family":"Hadjiyannis","sequence":"additional","affiliation":[{"name":"Thomas E. Starzl Transplantation Institute, University of Pittsburgh , Pittsburgh, PA,","place":["United States"]},{"name":"Department of Pathology, University of Pittsburgh , Pittsburgh, PA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey","family":"Camirand","sequence":"additional","affiliation":[{"name":"Thomas E. Starzl Transplantation Institute, University of Pittsburgh , Pittsburgh, PA,","place":["United States"]},{"name":"Department of Surgery, University of Pittsburgh , Pittsburgh, PA,","place":["United States"]},{"name":"Department of Immunology, University of Pittsburgh , Pittsburgh, PA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Geller","sequence":"additional","affiliation":[{"name":"Thomas E. Starzl Transplantation Institute, University of Pittsburgh , Pittsburgh, PA,","place":["United States"]},{"name":"Department of Surgery, University of Pittsburgh , Pittsburgh, PA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angus W","family":"Thomson","sequence":"additional","affiliation":[{"name":"Thomas E. Starzl Transplantation Institute, University of Pittsburgh , Pittsburgh, PA,","place":["United States"]},{"name":"Department of Surgery, University of Pittsburgh , Pittsburgh, PA,","place":["United States"]},{"name":"Department of Immunology, University of Pittsburgh , Pittsburgh, PA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"2026090201292678300_vkag224-B1","doi-asserted-by":"crossref","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines","volume":"7","author":"Th\u00e9ry","year":"2018","journal-title":"J Extracell Vesicles"},{"key":"2026090201292678300_vkag224-B2","doi-asserted-by":"crossref","first-page":"e12404","DOI":"10.1002\/jev2.12404","article-title":"Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches","volume":"13","author":"Welsh","year":"2024","journal-title":"J Extracell Vesicles"},{"key":"2026090201292678300_vkag224-B3","doi-asserted-by":"crossref","first-page":"eaau6977","DOI":"10.1126\/science.aau6977","article-title":"The biology, function, and biomedical applications of exosomes","volume":"367","author":"Kalluri","year":"2020","journal-title":"Science"},{"key":"2026090201292678300_vkag224-B4","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13578-019-0282-2","article-title":"Exosomes: biogenesis, biologic function and clinical potential","volume":"9","author":"Zhang","year":"2019","journal-title":"Cell 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mice","volume":"58","author":"Yoshida","year":"2013","journal-title":"Hepatology"},{"key":"2026090201292678300_vkag224-B23","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1055\/s-0038-1646949","article-title":"Hepatic dendritic cells, the tolerogenic liver environment, and liver disease","volume":"38","author":"Dou","year":"2018","journal-title":"Semin Liver Dis"},{"key":"2026090201292678300_vkag224-B24","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1002\/hep.30334","article-title":"DNAX activating protein of 12 kDa\/triggering receptor expressed on myeloid cells 2 expression by mouse and human liver dendritic cells: functional implications and regulation of liver ischemia-reperfusion injury","volume":"70","author":"Nakao","year":"2019","journal-title":"Hepatology"},{"key":"2026090201292678300_vkag224-B25","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0167-5699(98)01378-4","article-title":"Are dendritic cells the key to liver transplant 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