{"id":"https://openalex.org/W4391604157","doi":"https://doi.org/10.1016/j.jtct.2023.12.022","title":"Triggered: How Damage Induced IL-18 Suppresses Thymus Regeneration","display_name":"Triggered: How Damage Induced IL-18 Suppresses Thymus Regeneration","publication_year":2024,"publication_date":"2024-02-01","ids":{"openalex":"https://openalex.org/W4391604157","doi":"https://doi.org/10.1016/j.jtct.2023.12.022"},"language":"en","primary_location":{"id":"doi:10.1016/j.jtct.2023.12.022","doi":"https://doi.org/10.1016/j.jtct.2023.12.022","is_oa":true,"landing_page_url":"https://doi.org/10.1016/j.jtct.2023.12.022","pdf_url":null,"source":{"id":"https://openalex.org/S59987174","display_name":"Transplantation and Cellular Therapy","issn_l":"1083-8791","issn":["1083-8791","1523-6536","2666-6367"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-100","poland-20","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Transplantation and Cellular Therapy","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"hybrid","oa_url":"https://doi.org/10.1016/j.jtct.2023.12.022","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5091875786","display_name":"David W. Granadier","orcid":"https://orcid.org/0000-0002-1983-4190","observed_orcids":["https://orcid.org/0000-0002-1983-4190"]},"institutions":[{"id":"https://openalex.org/I4210089486","display_name":"Fred Hutch Cancer Center","ror":"https://ror.org/007ps6h72","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I4210089486"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"David Granadier","raw_affiliation_strings":["Fred Hutchinson Cancer Center, Seattle, WA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Fred Hutchinson Cancer Center, Seattle, WA","institution_ids":["https://openalex.org/I4210089486"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5050055062","display_name":"Kirsten Cooper","orcid":"https://orcid.org/0000-0002-0711-2713","observed_orcids":["https://orcid.org/0000-0002-0711-2713"]},"institutions":[{"id":"https://openalex.org/I4210089486","display_name":"Fred Hutch Cancer Center","ror":"https://ror.org/007ps6h72","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I4210089486"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Kirsten Cooper","raw_affiliation_strings":["Fred Hutchinson Cancer Center, Seattle, WA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Fred Hutchinson Cancer Center, Seattle, WA","institution_ids":["https://openalex.org/I4210089486"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5058991829","display_name":"Lorenzo Iovino","orcid":"https://orcid.org/0000-0002-3165-1899","observed_orcids":["https://orcid.org/0000-0002-3165-1899"]},"institutions":[{"id":"https://openalex.org/I4210089486","display_name":"Fred Hutch Cancer Center","ror":"https://ror.org/007ps6h72","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I4210089486"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Lorenzo Iovino","raw_affiliation_strings":["Fred Hutchinson Cancer Center, Seattle, WA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Fred Hutchinson Cancer Center, Seattle, WA","institution_ids":["https://openalex.org/I4210089486"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5034047540","display_name":"Dante Dennis Acenas II","orcid":"https://orcid.org/0000-0003-4137-0297","observed_orcids":["https://orcid.org/0000-0003-4137-0297"]},"institutions":[{"id":"https://openalex.org/I4210089486","display_name":"Fred Hutch Cancer Center","ror":"https://ror.org/007ps6h72","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I4210089486"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Dante V Acenas II","raw_affiliation_strings":["Fred Hutchinson Cancer Center, Seattle, WA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Fred Hutchinson Cancer Center, Seattle, WA","institution_ids":["https://openalex.org/I4210089486"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5066463475","display_name":"Paul C. DeRoos","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210089486","display_name":"Fred Hutch Cancer Center","ror":"https://ror.org/007ps6h72","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I4210089486"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Paul deRoos","raw_affiliation_strings":["Fred Hutchinson Cancer Center, Seattle, WA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Fred Hutchinson Cancer Center, Seattle, WA","institution_ids":["https://openalex.org/I4210089486"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5016053915","display_name":"Jarrod A. Dudakov","orcid":"https://orcid.org/0000-0001-6220-5632","observed_orcids":["https://orcid.org/0000-0001-6220-5632"]},"institutions":[{"id":"https://openalex.org/I4210089486","display_name":"Fred Hutch Cancer Center","ror":"https://ror.org/007ps6h72","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I4210089486"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jarrod A Dudakov","raw_affiliation_strings":["Fred Hutchinson Cancer Center, Seattle, WA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Fred Hutchinson Cancer Center, Seattle, WA","institution_ids":["https://openalex.org/I4210089486"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5091875786"],"corresponding_institution_ids":["https://openalex.org/I4210089486"],"apc_list":{"value":3650,"currency":"USD","value_usd":3650},"apc_paid":{"value":3650,"currency":"USD","value_usd":3650},"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.02107663,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"30","issue":"2","first_page":"S3","last_page":"S3"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10345","display_name":"Hematopoietic Stem Cell Transplantation","score":0.5536999702453613,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10345","display_name":"Hematopoietic Stem Cell Transplantation","score":0.5536999702453613,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10031","display_name":"T-cell and B-cell Immunology","score":0.38600000739097595,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11359","display_name":"Effects of Radiation Exposure","score":0.011099999770522118,"subfield":{"id":"https://openalex.org/subfields/2741","display_name":"Radiology, Nuclear Medicine and Imaging"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/thymus-regeneration","display_name":"thymus regeneration","score":0.9580000042915344},{"id":"https://openalex.org/keywords/il-18","display_name":"IL-18","score":0.9869999885559082},{"id":"https://openalex.org/keywords/il-18-receptor","display_name":"IL-18 receptor","score":0.7429999709129333},{"id":"https://openalex.org/keywords/natural-killer-cells","display_name":"natural killer cells","score":0.7020000219345093},{"id":"https://openalex.org/keywords/nkt-cells","display_name":"NKT cells","score":0.9369999766349792},{"id":"https://openalex.org/keywords/nk1-1","display_name":"NK1.1","score":0.656000018119812},{"id":"https://openalex.org/keywords/ionizing-radiation","display_name":"ionizing radiation","score":0.8040000200271606},{"id":"https://openalex.org/keywords/thymic-epithelial-cells","display_name":"thymic epithelial cells","score":0.8090000152587891},{"id":"https://openalex.org/keywords/thymic-stromal-lymphopoietin","display_name":"thymic stromal lymphopoietin","score":0.6119999885559082},{"id":"https://openalex.org/keywords/t-cell-reconstitution","display_name":"T cell reconstitution","score":0.7049999833106995},{"id":"https://openalex.org/keywords/perforin","display_name":"perforin","score":0.640999972820282},{"id":"https://openalex.org/keywords/cytotoxicity","display_name":"cytotoxicity","score":0.6800000071525574},{"id":"https://openalex.org/keywords/thymic-cellularity","display_name":"thymic cellularity","score":0.6299999952316284},{"id":"https://openalex.org/keywords/thymus","display_name":"thymus","score":0.4320000112056732}],"concepts":[{"id":"https://openalex.org/C171056886","wikidata":"https://www.wikidata.org/wiki/Q193119","display_name":"Regeneration (biology)","level":2,"score":0.7944788932800293},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.5857781767845154},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3713483214378357},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.36968523263931274}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1016/j.jtct.2023.12.022","doi":"https://doi.org/10.1016/j.jtct.2023.12.022","is_oa":true,"landing_page_url":"https://doi.org/10.1016/j.jtct.2023.12.022","pdf_url":null,"source":{"id":"https://openalex.org/S59987174","display_name":"Transplantation and Cellular Therapy","issn_l":"1083-8791","issn":["1083-8791","1523-6536","2666-6367"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-100","poland-20","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Transplantation and Cellular Therapy","raw_type":"journal-article"}],"best_oa_location":{"id":"doi:10.1016/j.jtct.2023.12.022","doi":"https://doi.org/10.1016/j.jtct.2023.12.022","is_oa":true,"landing_page_url":"https://doi.org/10.1016/j.jtct.2023.12.022","pdf_url":null,"source":{"id":"https://openalex.org/S59987174","display_name":"Transplantation and Cellular Therapy","issn_l":"1083-8791","issn":["1083-8791","1523-6536","2666-6367"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-100","poland-20","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Transplantation and Cellular Therapy","raw_type":"journal-article"},"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.98580002784729}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W4389233146","https://openalex.org/W4385685442","https://openalex.org/W4310099679","https://openalex.org/W4414131819","https://openalex.org/W7025160870","https://openalex.org/W3048933529","https://openalex.org/W2992538372","https://openalex.org/W3203498823","https://openalex.org/W3082545754","https://openalex.org/W4389243772"],"abstract_inverted_index":{"The":[0,18],"thymus":[1,19,55,146,171,278,297,366],"is":[2,20,152,197,219],"highly":[3,155],"sensitive":[4],"to":[5,43,61,76,102,136,245,310],"acute":[6,124],"injury":[7],"such":[8],"as":[9],"the":[10,149,191,223,235,296,339,375],"cytoreductive":[11],"conditioning":[12,74,355,371],"given":[13],"pre-hematopoietic":[14],"cell":[15,34,64,195,230,253,303,390,395],"transplant":[16],"(HCT).":[17],"capable":[21],"of":[22,26,45,54,84,105,107,143,163,204,226,248,255,322,341,360,377],"a":[23],"remarkable":[24],"degree":[25],"regeneration,":[27],"however":[28],"its":[29],"reparative":[30],"capacity":[31],"and":[32,47,87,141,159,261,273,382,388],"T":[33,63,394],"productivity":[35],"decline":[36],"with":[37,166],"age":[38],"leaving":[39],"HCT":[40,73],"recipients":[41],"vulnerable":[42],"relapse":[44],"malignancy":[46],"opportunistic":[48],"infection.":[49],"Better":[50],"understanding":[51],"endogenous":[52],"mechanisms":[53],"regeneration":[56,213,249,334],"may":[57,337,357,392],"inform":[58],"therapeutic":[59],"interventions":[60],"improve":[62,212,393],"reconstitution":[65,396],"in":[66,78,173,207,228,239,305,374],"these":[67,342,378],"patients.":[68],"Here,":[69],"we":[70,232,318,369],"report":[71],"that":[72,96,111,138,190,216,234,332,384],"leads":[75,101],"rises":[77],"immunogenic":[79],"cytokine":[80],"IL-18,":[81],"subsequent":[82],"activation":[83,140],"NK":[85,160,201,229,242,252,292,311,323,344,362,389],"cells":[86,206,243,293,312,363,381],"increased":[88,103,118],"cytotoxicity,":[89],"which":[90,188,364],"suppresses":[91,145,365],"organ":[92],"recovery.":[93,367],"We":[94,109],"observe":[95,319],"HCT-conditioning":[97,236,283],"by":[98,126,154,200],"ionizing":[99],"radiation":[100,265,329],"release":[104,142],"active":[106],"IL-18.":[108],"found":[110],"mice":[112,175,183,209,269],"deficient":[113,181,270],"for":[114,271,352],"IL-18":[115,144,220,227,240,373,387],"(Il18r1\u2212/\u2212)":[116],"exhibited":[117,276],"thymic":[119],"cellularity":[120,172,279],"one":[121],"week":[122],"following":[123,264,328],"damage":[125],"sublethal":[127],"irradiation":[128],"(SL-TBI)":[129],"(Fig.":[130,176],"1A":[131,177,285],"left).":[132],"This":[133],"led":[134],"us":[135],"conclude":[137],"post-damage":[139],"regeneration.":[147],"Within":[148],"thymus,":[150],"IL-18R":[151],"expressed":[153],"radioresistant":[156],"NK1.1+":[157,194,205],"NKT":[158,180],"cells.":[161,202,251,345],"Depletion":[162,203],"both":[164],"populations":[165],"anti-NK1.1":[167],"monoclonal":[168],"antibody":[169],"improved":[170,277],"WT":[174],"middle).":[178],"Notably,":[179],"CD1d\u2212/\u2212":[182],"showed":[184],"no":[185],"defective":[186],"repair":[187],"suggested":[189],"depletion":[192,196],"upon":[193],"largely":[198],"mediated":[199],"Il18r1\u2212/\u2212":[208],"did":[210],"not":[211,274],"further,":[214],"suggesting":[215,331],"NK-mediated":[217],"suppression":[218],"dependent.":[221],"Given":[222],"known":[224],"role":[225],"activation,":[231],"hypothesized":[233],"resultant":[237],"rise":[238],"stimulates":[241],"leading":[244],"\u201caccidental\u201d":[246],"targeting":[247,386],"promoting":[250,335],"production":[254],"cytotoxic":[256,380],"factors":[257],"including":[258],"IFNg,":[259],"GzmB":[260],"Perforin":[262,272],"increases":[263],"conditioning,":[266,330],"although":[267],"only":[268],"IFNg":[275],"7":[280],"days":[281],"post":[282],"(Fig":[284,315],"right).":[286],"Further":[287],"supporting":[288],"this":[289],"hypothesis,":[290],"IL-18R+CD49b+":[291],"isolated":[294,313],"from":[295],"2-days":[298],"post-irradiation":[299],"induced":[300,372],"more":[301],"target":[302],"death":[304],"head-to-head":[306],"cytotoxicity":[307,324,359,391],"assays":[308],"compared":[309],"pre-radiation":[314],"1B).":[316],"Finally,":[317],"TEC":[320],"downregulation":[321],"inhibitory":[325],"ligand":[326],"MHC-I":[327],"critical":[333],"stroma":[336],"be":[338],"targets":[340],"activated":[343],"These":[346],"findings":[347],"suggest":[348,383],"that,":[349],"while":[350],"necessary":[351],"successful":[353],"transplantation,":[354],"regimens":[356],"induce":[358],"bystander":[361],"Furthermore,":[368],"implicate":[370],"stimulation":[376],"suppressive":[379],"therapeutically":[385],"post-HCT.":[397]},"counts_by_year":[],"updated_date":"2026-10-12T09:40:04.860316","created_date":"2024-02-08T00:00:00"}