{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:31:14Z","timestamp":1790778674029,"version":"4.1.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T00:00:00Z","timestamp":1583193600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"DOI":"10.3389\/fimmu.2020.00302","type":"journal-article","created":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T04:40:30Z","timestamp":1583210430000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":32,"title":["Gender Disparity Impacts on Thymus Aging and LHRH Receptor Antagonist-Induced Thymic Reconstitution Following Chemotherapeutic Damage"],"prefix":"10.3389","volume":"11","author":[{"given":"Michael Ly","family":"Hun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kahlia","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine Rahma","family":"Gunawan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulaziz","family":"Alsharif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kylie","family":"Quinn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann P.","family":"Chidgey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,3,3]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1182\/blood.V84.7.2221.2221","article-title":"Lymphocyte depletion during treatment with intensive chemotherapy for cancer","volume":"84","author":"Mackall","year":"1994","journal-title":"Blood"},{"key":"B2","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1016\/j.ccell.2015.10.012","article-title":"Immunological effects of conventional chemotherapy and targeted anticancer agents","volume":"28","author":"Galluzzi","year":"2015","journal-title":"Cancer cell"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1093\/intimm\/dxm092","article-title":"Regeneration of the adult thymus is preceded by the expansion of K5+ K8+ epithelial cell progenitors and by increased expression of Trp63, cMyc and Tcf3 transcription factors in the thymic stroma","volume":"19","author":"Popa","year":"2007","journal-title":"Int Immunol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1007\/s00281-008-0140-5","article-title":"Strategies for reconstituting and boosting T cell-based immunity following haematopoietic stem cell transplantation: pre-clinical and clinical approaches","volume":"30","author":"Chidgey","year":"2008","journal-title":"Semin Immunopathol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"823","DOI":"10.4049\/jimmunol.0900225","article-title":"Ablation and regeneration of tolerance-inducing medullary thymic epithelial cells after cyclosporine, cyclophosphamide, and dexamethasone treatment","volume":"183","author":"Fletcher","year":"2009","journal-title":"J Immunol"},{"key":"B6","doi-asserted-by":"crossref","first-page":"6926","DOI":"10.4049\/jimmunol.162.11.6926","article-title":"Cyclosporin A-induced autologous graft-versus-host disease: a prototypical model of autoimmunity and active (dominant) tolerance coordinately induced by recent thymic emigrants","volume":"162","author":"Wu","year":"1999","journal-title":"J Immunol"},{"key":"B7","doi-asserted-by":"crossref","first-page":"3789","DOI":"10.1182\/blood.V90.9.3789","article-title":"Constraints on CD4 recovery postchemotherapy in adults: thymic insufficiency and apoptotic decline of expanded peripheral CD4 cells","volume":"90","author":"Hakim","year":"1997","journal-title":"Blood"},{"key":"B8","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1002\/path.2104","article-title":"Immunosenescence of aging","volume":"211","author":"Gruver","year":"2007","journal-title":"J Pathol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"8447","DOI":"10.1073\/pnas.0601040103","article-title":"Thymic output in aged mice","volume":"103","author":"Hale","year":"2006","journal-title":"Proc Natl Acad Sci USA"},{"key":"B10","doi-asserted-by":"publisher","first-page":"3887","DOI":"10.1016\/j.celrep.2019.05.045","article-title":"Interplay between Follistatin, Activin A, and BMP4 signaling regulates postnatal thymic epithelial progenitor cell differentiation during aging","volume":"27","author":"Lepletier","year":"2019","journal-title":"Cell Rep"},{"key":"B11","doi-asserted-by":"publisher","first-page":"12895","DOI":"10.1038\/srep12895","article-title":"Sex hormones have pervasive effects on thymic epithelial cells","volume":"5","author":"Dumont-Lagace","year":"2015","journal-title":"Sci Rep"},{"key":"B12","doi-asserted-by":"publisher","first-page":"2341","DOI":"10.1084\/jem.20131289","article-title":"Sex steroid blockade enhances thymopoiesis by modulating Notch signaling","volume":"211","author":"Velardi","year":"2014","journal-title":"J Exp Med"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1432","DOI":"10.1016\/j.celrep.2015.10.012","article-title":"Adult thymic medullary epithelium is maintained and regenerated by lineage-restricted cells rather than bipotent progenitors","volume":"13","author":"Ohigashi","year":"2015","journal-title":"Cell Rep"},{"key":"B14","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.it.2019.01.011","article-title":"Rethinking thymic tolerance: lessons from mice","volume":"40","author":"Inglesfield","year":"2019","journal-title":"Trends Immunol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1002\/eji.201344110","article-title":"Serial progression of cortical and medullary thymic epithelial microenvironments","volume":"44","author":"Alves","year":"2014","journal-title":"Eur J Immunol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"9885","DOI":"10.1073\/pnas.1301799110","article-title":"Aire-expressing thymic medullary epithelial cells originate from \u03b25t-expressing progenitor cells","volume":"110","author":"Ohigashi","year":"2013","journal-title":"PNAS"},{"key":"B17","doi-asserted-by":"publisher","first-page":"2819","DOI":"10.1016\/j.celrep.2016.02.080","article-title":"Identification of a bipotent epithelial progenitor population in the adult thymus","volume":"14","author":"Ulyanchenko","year":"2016","journal-title":"Cell Rep"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1016\/j.celrep.2014.07.029","article-title":"Multilineage potential and self-renewal define an epithelial progenitor cell population in the adult thymus","volume":"8","author":"Wong","year":"2014","journal-title":"Cell Rep"},{"key":"B19","doi-asserted-by":"publisher","first-page":"2741","DOI":"10.4049\/jimmunol.175.4.2741","article-title":"Activation of thymic regeneration in mice and humans following androgen blockade","volume":"175","author":"Sutherland","year":"2005","journal-title":"J Immunol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"4957","DOI":"10.2741\/2441","article-title":"Impact of androgen-deprivation therapy on the immune system: implications for combination therapy of prostate cancer","volume":"12","author":"Aragon-Ching","year":"2007","journal-title":"Front Biosci"},{"key":"B21","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/j.humimm.2010.02.007","article-title":"Prostate cancer patients on androgen deprivation therapy develop persistent changes in adaptive immune responses","volume":"71","author":"Morse","year":"2010","journal-title":"Hum Immunol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"6247","DOI":"10.4049\/jimmunol.0802446","article-title":"Withdrawal of sex steroids reverses age- and chemotherapy-related defects in bone marrow lymphopoiesis","volume":"182","author":"Dudakov","year":"2009","journal-title":"J Immunol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.it.2010.02.002","article-title":"Feeding the fire: the role of defective bone marrow function in exacerbating thymic involution","volume":"31","author":"Dudakov","year":"2010","journal-title":"Trends Immunol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"6014","DOI":"10.4049\/jimmunol.0802445","article-title":"Sex steroid ablation enhances immune reconstitution following cytotoxic antineoplastic therapy in young mice","volume":"184","author":"Goldberg","year":"2010","journal-title":"J Immunol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1210\/endo-125-2-1037","article-title":"Luteinizing hormone-releasing hormone (LHRH) agonist restoration of age-associated decline of thymus weight, thymic LHRH receptors, and thymocyte proliferative capacity","volume":"125","author":"Marchetti","year":"1989","journal-title":"Endocrinology"},{"key":"B26","doi-asserted-by":"publisher","first-page":"e42677","DOI":"10.1371\/journal.pone.0042677","article-title":"Impact of sex steroid ablation on viral, tumour and vaccine responses in aged mice","volume":"7","author":"Heng","year":"2012","journal-title":"PLoS ONE"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1158\/1078-0432.ccr-07-1784","article-title":"Enhanced immune system regeneration in humans following allogeneic or autologous hemopoietic stem cell transplantation by temporary sex steroid blockade","volume":"14","author":"Sutherland","year":"2008","journal-title":"Clin Cancer Res"},{"key":"B28","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1111\/j.1474-9726.2011.00773.x","article-title":"Persistent degenerative changes in thymic organ function revealed by an inducible model of organ regrowth","volume":"11","author":"Griffith","year":"2012","journal-title":"Aging Cell"},{"key":"B29","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":"B30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.biomaterials.2016.11.054","article-title":"Native thymic extracellular matrix improves in vivo thymic organoid T cell output, and drives in vitro thymic epithelial cell differentiation","volume":"118","author":"Hun","year":"2017","journal-title":"Biomaterials"},{"key":"B31","doi-asserted-by":"publisher","first-page":"87","DOI":"10.4103\/0976-500X.72350","article-title":"Blood sample collection in small laboratory animals","volume":"1","author":"Parasuraman","year":"2010","journal-title":"J Pharmacol Pharmacother"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.4049\/jimmunol.1701235","article-title":"Cellularity of thymic epithelial cells in the postnatal mouse","volume":"200","author":"Sakata","year":"2018","journal-title":"J Immunol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"3031","DOI":"10.1038\/s41467-019-10703-1","article-title":"Decreased maternal serum acetate and impaired fetal thymic and regulatory T cell development in preeclampsia","volume":"10","author":"Hu","year":"2019","journal-title":"Nat Commun"},{"key":"B34","doi-asserted-by":"publisher","first-page":"2982","DOI":"10.4049\/jimmunol.175.5.2982","article-title":"Effects of castration on thymocyte development in two different models of thymic involution","volume":"175","author":"Heng","year":"2005","journal-title":"J Immunol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"3512","DOI":"10.1016\/j.celrep.2018.05.057","article-title":"Age-related decline in primary CD8(+) T cell responses is associated with the development of senescence in virtual memory CD8(+) T cells","volume":"23","author":"Quinn","year":"2018","journal-title":"Cell Rep"},{"key":"B36","doi-asserted-by":"publisher","first-page":"7371","DOI":"10.4049\/jimmunol.176.12.7371","article-title":"Estrogen induces thymic atrophy by eliminating early thymic progenitors and inhibiting proliferation of beta-selected thymocytes","volume":"176","author":"Zoller","year":"2006","journal-title":"J Immunol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1210\/endo.139.2.5729","article-title":"Androgens accelerate thymocyte apoptosis","volume":"139","author":"Olsen","year":"1998","journal-title":"Endocrinology"},{"key":"B38","doi-asserted-by":"publisher","first-page":"600","DOI":"10.2353\/ajpath.2008.071008","article-title":"Sex differences in autoimmune disease from a pathological perspective","volume":"173","author":"Fairweather","year":"2008","journal-title":"Am J Pathol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"4641","DOI":"10.4049\/jimmunol.1501026","article-title":"Ectopic Aire expression in the thymic cortex reveals inherent properties of Aire as a tolerogenic factor within the medulla","volume":"195","author":"Nishijima","year":"2015","journal-title":"J Immunol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1084\/jem.20062497","article-title":"RANK signals from CD4(+)3(-) inducer cells regulate development of Aire-expressing epithelial cells in the thymic medulla","volume":"204","author":"Rossi","year":"2007","journal-title":"J Exp Med"},{"key":"B41","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":"B42","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1002\/eji.201646553","article-title":"A novel Foxn1(eGFP\/+) mouse model identifies Bmp4-induced maintenance of Foxn1 expression and thymic epithelial progenitor populations","volume":"47","author":"Barsanti","year":"2017","journal-title":"Eur J Immunol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"eaal2736","DOI":"10.1126\/sciimmunol.aal2736","article-title":"Production of BMP4 by endothelial cells is crucial for endogenous thymic regeneration","volume":"3","author":"Wertheimer","year":"2018","journal-title":"Sci Immunol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"4784","DOI":"10.4049\/jimmunol.1403158","article-title":"Young, proliferative thymic epithelial cells engraft and function in aging thymuses","volume":"194","author":"Kim","year":"2015","journal-title":"J Immunol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1038\/s41586-018-0346-1","article-title":"Single-cell mapping of the thymic stroma identifies IL-25-producing tuft epithelial cells","volume":"559","author":"Bornstein","year":"2018","journal-title":"Nature"},{"key":"B46","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1016\/j.immuni.2014.10.011","article-title":"Medullary thymic epithelial stem cells maintain a functional thymus to ensure lifelong central T cell tolerance","volume":"41","author":"Sekai","year":"2014","journal-title":"Immunity"},{"key":"B47","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1111\/imr.12412","article-title":"Medullary thymic epithelial stem cells: role in thymic epithelial cell maintenance and thymic involution","volume":"271","author":"Hamazaki","year":"2016","journal-title":"Immunol Rev"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.4049\/jimmunol.1701112","article-title":"Intrathymic deletion of IL-7 reveals a contribution of the bone marrow to thymic rebound induced by androgen blockade","volume":"200","author":"Rodrigues","year":"2018","journal-title":"J Immunol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1111\/j.1600-0897.1994.tb01119.x","article-title":"Effects of GnRH antagonist on lymphocyte subpopulations in primary and secondary lymphoid tissues of female mice","volume":"32","author":"Rao","year":"1994","journal-title":"Am J Reprod Immunol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"e12865","DOI":"10.1111\/acel.12865","article-title":"Lymph nodes as barriers to T-cell rejuvenation in aging mice and nonhuman primates","volume":"18","author":"Thompson","year":"2019","journal-title":"Aging Cell"},{"key":"B51","doi-asserted-by":"publisher","first-page":"2796","DOI":"10.1084\/jem.20181442","article-title":"CD49b defines functionally mature Treg cells that survey skin and vascular tissues","volume":"215","author":"Fan","year":"2018","journal-title":"J Exp Med"},{"key":"B52","doi-asserted-by":"publisher","first-page":"13498","DOI":"10.1073\/pnas.1307572110","article-title":"Virtual memory CD8 T cells display unique functional properties","volume":"110","author":"Lee","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"key":"B53","doi-asserted-by":"publisher","first-page":"4402","DOI":"10.1038\/s41467-019-11879-2","article-title":"Dynamic changes in epithelial cell morphology control thymic organ size during atrophy and regeneration","volume":"10","author":"Venables","year":"2019","journal-title":"Nat Commun"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2020.00302\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T00:25:41Z","timestamp":1695860741000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2020.00302\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,3]]},"references-count":53,"alternative-id":["10.3389\/fimmu.2020.00302"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2020.00302","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,3]]},"article-number":"302"}}