{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T15:13:01Z","timestamp":1724857981932},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2022,2,27]],"date-time":"2022-02-27T00:00:00Z","timestamp":1645920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2022,2,27]],"date-time":"2022-02-27T00:00:00Z","timestamp":1645920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2022,2,27]],"date-time":"2022-02-27T00:00:00Z","timestamp":1645920000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,9,30]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Three major subsets constitute the dendritic cells (DCs) pool in the thymus. They play key roles in self-antigen-specific thymocyte deletion and in the development of immunoregulatory T cells. Resident SIRPa\u2212 conventional DCs (cDCs, CD11c+PDCA1lo) are derived from intrathymic progenitors, whereas migratory SIRPa+ cDCs and plasmacytoid DCs (pDCs, CD11c+PDCA1+) originate from extrathymic sites. Here, we describe the organization and the shaping of cDC populations at the steady state and under stress conditions in wild-type and mutant mice (CD3eKO, IL7RaKO, and Flt3LKO). In neonates, the thymus is mainly composed of SIRPa\u2212-resident cDCs, whereas both cDC subsets are present in equal proportions in the adult. Upon thymus colonization, migratory SIRPa+ cDCs gain expression of phenotypic markers in a microenvironment dependent way. Here, we show that both processes are deeply impacted by mutations affecting T cell development. Under stress conditions such as sublethal irradiation, intrathymic resident SIRPa\u2212 cDCs are the first to regenerate the thymic cDC pool. Upon bone marrow transplantation, migratory SIRPa+ cDCs become the main source of thymic cDCs. These successive waves of regeneration eventually lead to a balance between resident and migratory DCs within the newly colonized thymus. These findings highlight an unrevealed division of labor between resident and migratory subsets for the organization\/establishment of the thymic cDC compartment.<\/jats:p>","DOI":"10.1002\/jlb.1a0921-502rr","type":"journal-article","created":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T07:14:41Z","timestamp":1646032481000},"page":"629-639","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Intrathymic SIRPa cDC subsets organization in normal and stress conditions reveal another level of cDCs heterogeneity"],"prefix":"10.1093","volume":"112","author":[{"given":"Victoria","family":"Michaels Lopez","sequence":"first","affiliation":[{"name":"Institut Necker Enfants Malades, Universit\u00e9 de Paris , Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agn\u00e8s","family":"Legrand","sequence":"additional","affiliation":[{"name":"Institut Necker Enfants Malades, Universit\u00e9 de Paris , Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuel","family":"Tejerina","sequence":"additional","affiliation":[{"name":"Institut Necker Enfants Malades, Universit\u00e9 de Paris , Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00e9rome","family":"Megret","sequence":"additional","affiliation":[{"name":"Structure F\u00e9d\u00e9rative de Recherche Necker , Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chantal","family":"Bordin","sequence":"additional","affiliation":[{"name":"Institut Necker Enfants Malades, Universit\u00e9 de Paris , Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V\u00e9ronique","family":"Quellec","sequence":"additional","affiliation":[{"name":"Institut Necker Enfants Malades, Universit\u00e9 de Paris , Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"Ezine","sequence":"additional","affiliation":[{"name":"Institut Necker Enfants Malades, Universit\u00e9 de Paris , Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,2,27]]},"reference":[{"key":"2023032107563541800_","doi-asserted-by":"crossref","first-page":"372","DOI":"10.4049\/jimmunol.177.1.372","article-title":"Signal regulatory protein molecules are differentially expressed by CD8- dendritic cells","volume":"177","author":"Lahoud","year":"2006","journal-title":"J Immunol"},{"key":"2023032107563541800_","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/349071a0","article-title":"CD4 expressed on earliest T-lineage precursor cells in the adult murine thymus","volume":"349","author":"Wu","year":"1991","journal-title":"Nature"},{"key":"2023032107563541800_","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1084\/jem.184.3.903","article-title":"Thymic dendritic cell precursors: relationship to the T lymphocyte lineage and phenotype of the dendritic cell progeny","volume":"184","author":"Wu","year":"1996","journal-title":"J Exp Med"},{"key":"2023032107563541800_","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1002\/eji.201141728","article-title":"The earliest intrathymic precursors of CD8\u03b1+ thymic dendritic cells correspond to myeloid-type double-negative 1c cells","volume":"41","author":"Luche","year":"2011","journal-title":"Eur J Immunol"},{"key":"2023032107563541800_","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1242\/dev.069344","article-title":"Transcriptional priming of intrathymic precursors for dendritic cell development","volume":"139","author":"Moore","year":"2012","journal-title":"Development"},{"key":"2023032107563541800_","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1126\/science.1178331","article-title":"Development of monocytes, macrophages, and dendritic cells","volume":"327","author":"Geissmann","year":"2010","journal-title":"Science"},{"key":"2023032107563541800_","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/ni1462","article-title":"Origin of dendritic cells in peripheral lymphoid organs of mice","volume":"8","author":"Liu","year":"2007","journal-title":"Nat Immunol"},{"key":"2023032107563541800_","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1084\/jem.20082232","article-title":"Thymus-homing peripheral dendritic cells constitute two of the three major subsets of dendritic cells in the steady-state thymus","volume":"206","author":"Li","year":"2009","journal-title":"J Exp Med"},{"key":"2023032107563541800_","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1038\/ni1385","article-title":"Clonal deletion of thymocytes by circulating dendritic cells homing to the thymus","volume":"7","author":"Bonasio","year":"2006","journal-title":"Nat Immunol"},{"key":"2023032107563541800_","doi-asserted-by":"crossref","first-page":"19869","DOI":"10.1073\/pnas.0810268105","article-title":"Dendritic cells in the thymus contribute to T-regulatory cell induction","volume":"105","author":"Proietto","year":"2008","journal-title":"Proc Natl Acad Sci USA."},{"key":"2023032107563541800_","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1084\/jem.20102327","article-title":"Aire-dependent production of XCL1 mediates medullary accumulation of thymic dendritic cells and contributes to regulatory T cell development","volume":"208","author":"Lei","year":"2011","journal-title":"J Exp Med"},{"key":"2023032107563541800_","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1084\/jem.20082449","article-title":"The thymic medulla: a unique microenvironment for intercellular self-antigen transfer","volume":"206","author":"Koble","year":"2009","journal-title":"J Exp Med"},{"key":"2023032107563541800_","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1084\/jem.20041457","article-title":"Central tolerance to tissue-specific antigens mediated by direct and indirect antigen presentation","volume":"200","author":"Gallegos","year":"2004","journal-title":"J Exp Med"},{"key":"2023032107563541800_","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1002\/eji.201243192","article-title":"Thymus-homing dendritic cells in central tolerance","volume":"43","author":"Hadeiba","year":"2013","journal-title":"Eur J Immunol"},{"key":"2023032107563541800_","doi-asserted-by":"crossref","first-page":"3053","DOI":"10.4049\/jimmunol.0900438","article-title":"Crucial contribution of thymic Sirp alpha+ conventional dendritic cells to central tolerance against blood-borne antigens in a CCR2-dependent manner","volume":"183","author":"Baba","year":"2009","journal-title":"J Immunol"},{"key":"2023032107563541800_","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.celrep.2017.09.016","article-title":"CCR7 modulates the generation of thymic regulatory T cells by altering the composition of the thymic dendritic cell compartment","volume":"21","author":"Hu","year":"2017","journal-title":"Cell Rep"},{"key":"2023032107563541800_","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/j.immuni.2016.08.013","article-title":"IRF8 transcription factor controls survival and function of terminally differentiated conventional and plasmacytoid dendritic cells, respectively","volume":"45","author":"Sichien","year":"2016","journal-title":"Immunity."},{"key":"2023032107563541800_","doi-asserted-by":"crossref","first-page":"3368","DOI":"10.4049\/jimmunol.1102613","article-title":"IRF4 promotes cutaneous dendritic cell migration to lymph nodes during homeostasis and inflammation","volume":"189","author":"Baja\u00f1a","year":"2012","journal-title":"J Immunol"},{"key":"2023032107563541800_","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1084\/jem.186.9.1535","article-title":"Interferon (IFN) consensus sequence-binding protein, a transcription factor of the IFN regulatory factor family, regulates immune responses in vivo through control of interleukin 12 expression","volume":"186","author":"Giese","year":"1997","journal-title":"J Exp Med"},{"key":"2023032107563541800_","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.4049\/jimmunol.163.4.2000","article-title":"Roles of IFN consensus sequence binding protein and PU.1 in regulating IL-18 gene expression","volume":"163","author":"Kim","year":"1999","journal-title":"J Immunol"},{"key":"2023032107563541800_","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1084\/jem.20011128","article-title":"Interferon regulatory factor 4 (IRF4) interacts with NFATc2 to modulate interleukin 4 gene expression","volume":"195","author":"Rengarajan","year":"2002","journal-title":"J Exp Med"},{"key":"2023032107563541800_","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1038\/s41467-018-03619-9","article-title":"Lymphotoxin \u03b1 fine-tunes T cell clonal deletion by regulating thymic entry of antigen-presenting cells","volume":"9","author":"Lopes","year":"2018","journal-title":"Nat Commun"},{"key":"2023032107563541800_","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.4049\/jimmunol.172.2.1018","article-title":"Development of the dendritic cell system during mouse ontogeny","volume":"172","author":"Dakic","year":"2004","journal-title":"J Immunol"},{"key":"2023032107563541800_","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1084\/jem.20021263","article-title":"ICSBP is essential for the development of mouse type I interferon-producing cells and for the generation and activation of CD8alpha(+) dendritic cells","volume":"196","author":"Schiavoni","year":"2002","journal-title":"J Exp Med"},{"key":"2023032107563541800_","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.4049\/jimmunol.174.5.2573","article-title":"IFN regulatory factor-4 and -8 govern dendritic cell subset development and their functional diversity","volume":"174","author":"Tamura","year":"2005","journal-title":"J Immunol"},{"key":"2023032107563541800_","doi-asserted-by":"crossref","first-page":"8981","DOI":"10.1073\/pnas.0402139101","article-title":"Critical roles of interferon regulatory factor 4 in CD11bhighCD8alpha- dendritic cell development","volume":"101","author":"Suzuki","year":"2004","journal-title":"Proc Natl Acad Sci USA."},{"key":"2023032107563541800_","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.4049\/jimmunol.173.3.1604","article-title":"Regulation of thymus size by competition for stromal niches among early T cell progenitors","volume":"173","author":"Prockop","year":"2004","journal-title":"J Immunol"}],"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/JLB.1A0921-502RR","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/JLB.1A0921-502RR","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/112\/4\/629\/49471725\/jlb11099.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/112\/4\/629\/49471725\/jlb11099.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T05:15:50Z","timestamp":1700284550000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/112\/4\/629\/6976179"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,27]]},"references-count":27,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,2,27]]},"published-print":{"date-parts":[[2022,9,30]]}},"URL":"https:\/\/doi.org\/10.1002\/jlb.1a0921-502rr","relation":{},"ISSN":["0741-5400","1938-3673"],"issn-type":[{"value":"0741-5400","type":"print"},{"value":"1938-3673","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,10]]},"published":{"date-parts":[[2022,2,27]]},"assertion":[{"value":"2021-08-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}