{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T13:32:28Z","timestamp":1791639148928,"version":"4.3.4"},"reference-count":37,"publisher":"American Society for Clinical Investigation","issue":"4","license":[{"start":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T00:00:00Z","timestamp":1740355200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01HL167901,K23 HL151750,R01HL146519,S10OD028483"],"award-info":[{"award-number":["R01HL167901,K23 HL151750,R01HL146519,S10OD028483"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,24]]},"abstract":"<jats:p>\n                    Chronic lung allograft dysfunction (CLAD) substantially limits long-term survival following lung transplantation. To identify potential targets for CLAD prevention, T cells from explanted CLAD lungs and lung-draining lymph nodes, as well as diseased and nondiseased controls were isolated and single-cell RNA sequencing and TCR sequencing were performed. TCR sequencing revealed a clonally expanded population of CD8\n                    <jats:sup>+<\/jats:sup>\n                    tissue-resident memory T cells (TRMs) with high cytotoxic potential, including upregulation of\n                    <jats:italic>KLRK1<\/jats:italic>\n                    , encoding the co-receptor NKG2D. These cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    TRMs accumulated around the CLAD airways and had a 100-fold increase in clonal overlap with lung-draining lymph nodes when compared with non-CLAD lungs. Using a murine model of orthotopic lung transplantation, we confirmed that cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    TRM accumulation was due to chronic rejection and not transplantation alone. Furthermore, blocking NKG2D in vivo attenuated the airway remodeling following transplantation and diminished airway accumulation of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Our findings support NKG2D as a potential therapeutic target for CLAD, affecting cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    TRM accumulation.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.184048","type":"journal-article","created":{"date-parts":[[2025,2,23]],"date-time":"2025-02-23T14:00:45Z","timestamp":1740319245000},"source":"Crossref","is-referenced-by-count":15,"title":["NKG2D blockade impairs tissue-resident memory T cell accumulation and reduces chronic lung allograft dysfunction"],"prefix":"10.1172","volume":"10","author":[{"given":"Kaveh","family":"Moghbeli","sequence":"first","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline A.","family":"Lipp","sequence":"additional","affiliation":[{"name":"Department of Pharmacy,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7140-9899","authenticated-orcid":true,"given":"Marta","family":"Bueno","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3524-2029","authenticated-orcid":true,"given":"Andrew","family":"Craig","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Rojas","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minahal","family":"Abbas","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary I.","family":"Lakkis","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byron","family":"Chuan","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4108-803X","authenticated-orcid":true,"given":"John","family":"Sembrat","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8921-1944","authenticated-orcid":true,"given":"Kentaro","family":"Noda","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Kass","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Oury","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihe","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0595-595X","authenticated-orcid":true,"given":"John F.","family":"McDyer","sequence":"additional","affiliation":[{"name":"Department of Medicine,"},{"name":"Starzl Transplantation Institute, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7170-0360","authenticated-orcid":true,"given":"Oliver","family":"Eickelberg","sequence":"additional","affiliation":[{"name":"Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0092-9296","authenticated-orcid":true,"given":"Mark E.","family":"Snyder","sequence":"additional","affiliation":[{"name":"Department of Medicine,"},{"name":"Starzl Transplantation Institute, Pittsburgh, Pennsylvania, USA."},{"name":"Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2025,2,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2019.03.009"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.16463"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.119.006218"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0135972"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.167082"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aav5581"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20212059"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.10.026"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2009.02742.x"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/v13122359"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02549"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.156648"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.124732"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2010-0099RC"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803514"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2007.01756.x"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajt.2024.02.020"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20200218"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2011.03663.x"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200911-1786OC"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.12.002"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2018-212345"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202303-0472OC"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.164603"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.06.014"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201209-1749OC"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.16360"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.677707"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.11.005"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abo0686"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021484"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2011.03466.x"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4096"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.22139.1"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1874-1"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4314"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.123971"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/184048\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T20:26:43Z","timestamp":1779136003000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/184048"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,24]]},"references-count":37,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,1,7]]},"published-print":{"date-parts":[[2025,2,24]]}},"alternative-id":["10.1172\/jci.insight.184048"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.184048","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,24]]},"article-number":"e184048"}}