{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T22:27:09Z","timestamp":1783636029932,"version":"3.55.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T00:00:00Z","timestamp":1719273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for Promotion of Science","doi-asserted-by":"crossref","award":["KAKENHI 19H03485, 19H04802, 21H05046, 21K18254, 22H02886"],"award-info":[{"award-number":["KAKENHI 19H03485, 19H04802, 21H05046, 21K18254, 22H02886"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["23gm1210008"],"award-info":[{"award-number":["23gm1210008"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The thymus is an organ required for T cell development and is also an eosinophil-rich organ; however, the nature and function of thymic eosinophils remain unclear. Here, we characterized the gene expression and differentiation mechanism of thymic eosinophils in mice. Thymic eosinophils showed a distinct gene expression profile compared with other organ-resident eosinophils. The number of thymic eosinophils was controlled by medullary thymic epithelial cells (mTECs). In Rag-deficient mice, the unique gene expression signature of thymic eosinophils was lost but restored by pre-T cell receptor signalling, which induces CD4+ CD8+ thymocyte differentiation, indicating that T cell differentiation beyond the CD4\u2212 CD8\u2212 stage is necessary and sufficient for the induction of thymic eosinophils. These results demonstrate that thymic eosinophils are quantitatively and qualitatively regulated by mTECs and developing thymocytes, respectively, suggesting that thymic eosinophils are a distinct, thymus-specific cell subset, induced by interactions with thymic cells.<\/jats:p>","DOI":"10.1093\/intimm\/dxae037","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T10:12:55Z","timestamp":1719310375000},"page":"617-628","source":"Crossref","is-referenced-by-count":6,"title":["Synchronized development of thymic eosinophils and thymocytes"],"prefix":"10.1093","volume":"36","author":[{"given":"Ayami","family":"Ota","sequence":"first","affiliation":[{"name":"The University of Tokyo Department of Immunology, Graduate School of Medicine and Faculty of Medicine, , Tokyo 113-0033 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Iguchi","sequence":"additional","affiliation":[{"name":"The University of Tokyo Department of Immunology, Graduate School of Medicine and Faculty of Medicine, , Tokyo 113-0033 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachiko","family":"Nitta","sequence":"additional","affiliation":[{"name":"The University of Tokyo Department of Immunology, Graduate School of Medicine and Faculty of Medicine, , Tokyo 113-0033 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryunosuke","family":"Muro","sequence":"additional","affiliation":[{"name":"The University of Tokyo Department of Immunology, Graduate School of Medicine and Faculty of Medicine, , Tokyo 113-0033 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanami","family":"Mino","sequence":"additional","affiliation":[{"name":"The University of Tokyo Department of Immunology, Graduate School of Medicine and Faculty of Medicine, , Tokyo 113-0033 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Tsukasaki","sequence":"additional","affiliation":[{"name":"The University of Tokyo Department of Osteoimmunology, Graduate School of Medicine and Faculty of Medicine, , Tokyo 113-0033 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8194-3777","authenticated-orcid":false,"given":"Josef M","family":"Penninger","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA) , Vienna ,","place":["Austria"]},{"name":"The University of British Columbia Department of Medical Genetics, Life Sciences Institute, , Vancouver, British Columbia,","place":["Canada"]},{"name":"Department of Innovative Organoid Research, Helmholtz Centre for Infection Research , Braunschweig ,","place":["Germany"]},{"name":"Eric Kandel Institute, Department of Laboratory Medicine, Medical University Vienna , Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2384-3062","authenticated-orcid":false,"given":"Takeshi","family":"Nitta","sequence":"additional","affiliation":[{"name":"The University of Tokyo Department of Immunology, Graduate School of Medicine and Faculty of Medicine, , Tokyo 113-0033 ,","place":["Japan"]},{"name":"Tokyo University of Science Division of Molecular Pathology, Research Institute for Biomedical Sciences, , Chiba 278-0022 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Takayanagi","sequence":"additional","affiliation":[{"name":"The University of Tokyo Department of Immunology, Graduate School of Medicine and Faculty of Medicine, , Tokyo 113-0033 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,6,25]]},"reference":[{"key":"2024112205262284500_CIT0001","doi-asserted-by":"publisher","first-page":"eaba2429","DOI":"10.1126\/science.aba2429","article-title":"The function of the thymus and its impact on modern medicine","volume":"369","author":"Miller","year":"2020","journal-title":"Science"},{"key":"2024112205262284500_CIT0002","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1038\/nri3667","article-title":"Positive and negative selection of the T cell repertoire: what thymocytes see (and don\u2019t see)","volume":"14","author":"Klein","year":"2014","journal-title":"Nat Rev Immunol"},{"key":"2024112205262284500_CIT0003","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1146\/annurev-immunol-051116-052320","article-title":"Thymic epithelial cells","volume":"35","author":"Abramson","year":"2017","journal-title":"Annu Rev Immunol"},{"key":"2024112205262284500_CIT0004","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1038\/nri.2017.12","article-title":"Generation of diversity in thymic epithelial cells","volume":"17","author":"Takahama","year":"2017","journal-title":"Nat Rev Immunol"},{"key":"2024112205262284500_CIT0005","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/nri3341","article-title":"Eosinophils: changing perspectives in health and disease","volume":"13","author":"Rosenberg","year":"2013","journal-title":"Nat Rev Immunol"},{"key":"2024112205262284500_CIT0006","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1038\/nri.2017.95","article-title":"Functions of tissue-resident eosinophils","volume":"17","author":"Weller","year":"2017","journal-title":"Nat Rev Immunol"},{"key":"2024112205262284500_CIT0007","doi-asserted-by":"publisher","first-page":"101","DOI":"10.3389\/fmed.2017.00101","article-title":"Homeostatic eosinophils: characteristics and functions","volume":"4","author":"Marichal","year":"2017","journal-title":"Front Med"},{"key":"2024112205262284500_CIT0008","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1038\/s41385-020-0281-y","article-title":"The emerging roles of eosinophils in mucosal homeostasis","volume":"13","author":"Shah","year":"2020","journal-title":"Mucosal Immunol"},{"key":"2024112205262284500_CIT0009","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1084\/jem.20141388","article-title":"Small intestinal eosinophils regulate Th17 cells by producing IL-1 receptor antagonist","volume":"213","author":"Sugawara","year":"2016","journal-title":"J Exp Med"},{"key":"2024112205262284500_CIT0010","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1016\/j.immuni.2016.10.031","article-title":"Perinatal activation of the interleukin-33 pathway promotes type 2 immunity in the developing lung","volume":"45","author":"de Kleer","year":"2016","journal-title":"Immunity"},{"key":"2024112205262284500_CIT0011","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1182\/blood-2013-05-502443","article-title":"Activated mouse eosinophils protect against lethal respiratory virus infection","volume":"123","author":"Percopo","year":"2014","journal-title":"Blood"},{"key":"2024112205262284500_CIT0012","doi-asserted-by":"publisher","first-page":"3279","DOI":"10.1172\/JCI85664","article-title":"Lung-resident eosinophils represent a distinct regulatory eosinophil subset","volume":"126","author":"Mesnil","year":"2016","journal-title":"J Clin Invest"},{"key":"2024112205262284500_CIT0013","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.4049\/jimmunol.165.4.1965","article-title":"CD11c+ eosinophils in the murine thymus: developmental regulation and recruitment upon MHC class I-restricted thymocyte deletion","volume":"165","author":"Throsby","year":"2000","journal-title":"J Immunol"},{"key":"2024112205262284500_CIT0014","doi-asserted-by":"publisher","first-page":"e11439","DOI":"10.1371\/journal.pone.0011439","article-title":"Selective depletion of eosinophils or neutrophils in mice impacts the efficiency of apoptotic cell clearance in the thymus","volume":"5","author":"Kim","year":"2010","journal-title":"PLoS One"},{"key":"2024112205262284500_CIT0015","doi-asserted-by":"publisher","first-page":"2043","DOI":"10.2353\/ajpath.2009.090015","article-title":"Thymic indoleamine 2,3-dioxygenase-positive eosinophils in young children","volume":"175","author":"Tulic","year":"2009","journal-title":"Am J Pathol"},{"key":"2024112205262284500_CIT0016","doi-asserted-by":"publisher","first-page":"5909","DOI":"10.4049\/jimmunol.173.10.5909","article-title":"Cutting edge: human eosinophils regulate T cell subset selection through indoleamine 2,3-dioxygenase","volume":"173","author":"Odemuyiwa","year":"2004","journal-title":"J Immunol"},{"key":"2024112205262284500_CIT0017","doi-asserted-by":"publisher","first-page":"eabn3286","DOI":"10.1126\/sciimmunol.abn3286","article-title":"Eosinophils are an essential element of a type 2 immune axis that controls thymus regeneration","volume":"7","author":"Cosway","year":"2022","journal-title":"Sci Immunol"},{"key":"2024112205262284500_CIT0018","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1002\/eji.202049080","article-title":"Eosinophils interact with thymocytes and proliferate in the human thymus","volume":"51","author":"Albinsson","year":"2021","journal-title":"Eur J Immunol"},{"key":"2024112205262284500_CIT0019","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1111\/imm.13610","article-title":"Distinct populations of eosinophils in the human thymus with capacity to modulate thymocyte maturation","volume":"169","author":"Albinsson","year":"2022","journal-title":"Immunology"},{"key":"2024112205262284500_CIT0020","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/1471-213X-7-69","article-title":"Specific expression of lacZ and Cre recombinase in fetal thymic epithelial cells by multiplex gene targeting at the Foxn1 locus","volume":"7","author":"Gordon","year":"2007","journal-title":"BMC Dev Biol"},{"key":"2024112205262284500_CIT0021","doi-asserted-by":"publisher","first-page":"108124","DOI":"10.1016\/j.celrep.2020.108124","article-title":"OPG production matters where it happened","volume":"32","author":"Tsukasaki","year":"2020","journal-title":"Cell Reports"},{"key":"2024112205262284500_CIT0022","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1038\/nature08596","article-title":"Central control of fever and female body temperature by RANKL\/RANK","volume":"462","author":"Hanada","year":"2009","journal-title":"Nature"},{"key":"2024112205262284500_CIT0023","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/1074-7613(94)90095-7","article-title":"The immune responses in CD40-deficient mice: impaired immunoglobulin class switching and germinal center formation","volume":"1","author":"Kawabe","year":"1994","journal-title":"Immunity"},{"key":"2024112205262284500_CIT0024","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1016\/0092-8674(92)90030-g","article-title":"RAG-1-deficient mice have no mature B and T lymphocytes","volume":"68","author":"Mombaerts","year":"1992","journal-title":"Cell"},{"key":"2024112205262284500_CIT0025","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1126\/science.8430336","article-title":"Restoration of T cell development in RAG-2-deficient mice by functional TCR transgenes","volume":"259","author":"Shinkai","year":"1993","journal-title":"Science"},{"key":"2024112205262284500_CIT0026","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/360225a0","article-title":"Mutations in T-cell antigen receptor genes alpha and beta block thymocyte development at different stages","volume":"360","author":"Mombaerts","year":"1992","journal-title":"Nature"},{"key":"2024112205262284500_CIT0027","doi-asserted-by":"publisher","first-page":"638","DOI":"10.15252\/embr.201540096","article-title":"The thymic cortical epithelium determines the TCR repertoire of IL-17-producing \u03b3\u03b4T cells","volume":"16","author":"Nitta","year":"2015","journal-title":"EMBO Rep"},{"key":"2024112205262284500_CIT0028","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.jim.2012.07.023","article-title":"Purified enzymes improve isolation and characterization of the adult thymic epithelium","volume":"385","author":"Seach","year":"2012","journal-title":"J Immunol Methods"},{"key":"2024112205262284500_CIT0029","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","article-title":"Metascape provides a biologist-oriented resource for the analysis of systems-level datasets","volume":"10","author":"Zhou","year":"2019","journal-title":"Nat Commun"},{"key":"2024112205262284500_CIT0030","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","article-title":"Integrated analysis of multimodal single-cell data","volume":"184","author":"Hao","year":"2021","journal-title":"Cell"},{"key":"2024112205262284500_CIT0031","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1093\/jleuko\/qiad064","article-title":"MHCII+CD80+ thymic eosinophils increase in abundance during neonatal development in mice and their accumulation is microbiota-dependent","volume":"114","author":"Gatti","year":"2023","journal-title":"J Leukoc Biol"},{"key":"2024112205262284500_CIT0032","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/j.immuni.2008.06.015","article-title":"The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance","volume":"29","author":"Akiyama","year":"2008","journal-title":"Immunity"},{"key":"2024112205262284500_CIT0033","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1016\/j.immuni.2008.06.018","article-title":"The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator","volume":"29","author":"Hikosaka","year":"2008","journal-title":"Immunity"},{"key":"2024112205262284500_CIT0034","doi-asserted-by":"publisher","first-page":"6273","DOI":"10.1073\/pnas.95.11.6273","article-title":"Eotaxin is required for the baseline level of tissue eosinophils","volume":"95","author":"Matthews","year":"1998","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024112205262284500_CIT0035","doi-asserted-by":"publisher","first-page":"498","DOI":"10.4049\/jimmunol.1500558","article-title":"Differential features of AIRE-induced and AIRE-independent promiscuous gene expression in thymic epithelial cells","volume":"195","author":"St-Pierre","year":"2015","journal-title":"J Immunol"},{"key":"2024112205262284500_CIT0036","doi-asserted-by":"publisher","first-page":"e101828","DOI":"10.15252\/embj.2019101828","article-title":"Biologically indeterminate yet ordered promiscuous gene expression in single medullary thymic epithelial cells","volume":"39","author":"Dhalla","year":"2020","journal-title":"EMBO J"},{"key":"2024112205262284500_CIT0037","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1146\/annurev.immunol.24.021605.090720","article-title":"The eosinophil","volume":"24","author":"Rothenberg","year":"2006","journal-title":"Annu Rev Immunol"},{"key":"2024112205262284500_CIT0038","doi-asserted-by":"publisher","first-page":"e20210970","DOI":"10.1084\/jem.20210970","article-title":"The aryl hydrocarbon receptor contributes to tissue adaptation of intestinal eosinophils in mice","volume":"219","author":"Diny","year":"2022","journal-title":"J Exp Med"},{"key":"2024112205262284500_CIT0039","doi-asserted-by":"publisher","first-page":"40","DOI":"10.4049\/jimmunol.2200609","article-title":"Diversity in cortical thymic epithelial cells occurs through loss of a Foxn1-dependent gene signature driven by stage-specific thymocyte cross-talk","volume":"210","author":"White","year":"2023","journal-title":"J Immunol"},{"key":"2024112205262284500_CIT0040","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1182\/blood-2005-03-0998","article-title":"The transcription factor Gli3 regulates differentiation of fetal CD4","volume":"106","author":"Hager-Theodorides","year":"2005","journal-title":"Blood"},{"key":"2024112205262284500_CIT0041","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1093\/intimm\/9.10.1475","article-title":"Pre-TCR signaling components trigger transcriptional activation of a rearranged TCR alpha gene locus and silencing of the pre-TCR alpha locus: implications for intrathymic differentiation","volume":"9","author":"Koyasu","year":"1997","journal-title":"Int Immunol"},{"key":"2024112205262284500_CIT0042","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1084\/jem.185.4.785","article-title":"Targeted disruption of the chemokine eotaxin partially reduces antigen-induced tissue eosinophilia","volume":"185","author":"Rothenberg","year":"1997","journal-title":"J Exp Med"},{"key":"2024112205262284500_CIT0043","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1038\/s41590-020-0756-8","article-title":"Fibroblasts as a source of self-antigens for central immune tolerance","volume":"21","author":"Nitta","year":"2020","journal-title":"Nat Immunol"},{"key":"2024112205262284500_CIT0044","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1016\/j.immuni.2015.05.013","article-title":"Thymic B cells are licensed to present self antigens for central T cell tolerance induction","volume":"42","author":"Yamano","year":"2015","journal-title":"Immunity"},{"key":"2024112205262284500_CIT0045","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1038\/s41590-022-01218-x","article-title":"Type 2 cytokines in the thymus activate Sirp\u03b1+ dendritic cells to promote clonal deletion","volume":"23","author":"Breed","year":"2022","journal-title":"Nat Immunol"},{"key":"2024112205262284500_CIT0046","doi-asserted-by":"publisher","first-page":"2542","DOI":"10.1016\/j.cell.2022.05.018","article-title":"Thymic epithelial cells co-opt lineage-defining transcription factors to eliminate autoreactive T cells","volume":"185","author":"Michelson","year":"2022","journal-title":"Cell"}],"container-title":["International Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/intimm\/advance-article-pdf\/doi\/10.1093\/intimm\/dxae037\/58413071\/dxae037.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/intimm\/article-pdf\/36\/12\/617\/60783033\/dxae037.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/intimm\/article-pdf\/36\/12\/617\/60783033\/dxae037.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T05:28:02Z","timestamp":1732253282000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/intimm\/article\/36\/12\/617\/7698229"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,25]]},"references-count":46,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,6,25]]},"published-print":{"date-parts":[[2024,11,14]]}},"URL":"https:\/\/doi.org\/10.1093\/intimm\/dxae037","relation":{},"ISSN":["1460-2377"],"issn-type":[{"value":"1460-2377","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,12]]},"published":{"date-parts":[[2024,6,25]]}}}