Partridge L, Deelen J, Slagboom PE. Facing up to the global challenges of ageing. Nature. 2018;561:45–56. https://doi.org/10.1038/s41586-018-0457-8.

Article  CAS  PubMed  Google Scholar 

Lepletier A, Chidgey AP, Savino W. Perspectives for improvement of the thymic microenvironment through manipulation of thymic epithelial cells: a mini-review. Gerontology. 2015;61:504–14. https://doi.org/10.1159/000375160.

Article  CAS  PubMed  Google Scholar 

Palmer S, Albergante L, Blackburn CC, Newman TJ. Thymic involution and rising disease incidence with age. Proc Natl Acad Sci U S A. 2018;115:1883–8. https://doi.org/10.1073/pnas.1714478115.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Min H, Montecino-Rodriguez E, Dorshkind K. Reduction in the developmental potential of intrathymic T cell progenitors with age. J Immunol. 2004;173:245–50. https://doi.org/10.4049/jimmunol.173.1.245.

Article  CAS  PubMed  Google Scholar 

Gui J, Zhu X, Dohkan J, Cheng L, Barnes PF, Su DM. The aged thymus shows normal recruitment of lymphohematopoietic progenitors but has defects in thymic epithelial cells. Int Immunol. 2007;19:1201–11. https://doi.org/10.1093/intimm/dxm095.

Article  CAS  PubMed  Google Scholar 

Zhu X, Gui J, Dohkan J, Cheng L, Barnes PF, Su DM. Lymphohematopoietic progenitors do not have a synchronized defect with age-related thymic involution. Aging Cell. 2007;6:663–72. https://doi.org/10.1111/j.1474-9726.2007.00325.x.

Article  CAS  PubMed  Google Scholar 

Mackall CL, Punt JA, Morgan P, Farr AG, Gress RE. Thymic function in young/old chimeras: substancial thymic T cell regenerative capacity despite irreversible age-associated thymic involution. J Immunol. 1998;28:1886–93. https://doi.org/10.1002/(SICI)1521-4141(199806)28:06%3c1886::AID-IMMU1886%3e3.0.CO;2-M.

Article  CAS  Google Scholar 

Min D, Panoskaltsis-Mortari A, Kuro-o M, Holländer GA, Blazar BR, Weinberg KI. Sustained thymopoiesis and improvement in functional immunity induced by exogenous KGF administration in murine models of aging. Blood. 2007;109:2529–37. https://doi.org/10.1182/blood-2006-08-043794.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Taub DD, Murphy WJ, Longo DL. Rejuvenation of the aging thymus: growth hormone-mediated and ghrelin-mediated signaling pathways. Curr Opin Pharmacol. 2010;10:408–24. https://doi.org/10.1016/j.coph.2010.04.015.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chiu H, Linsley PS, Ziegler SF. Investigating thymic epithelial cell diversity using systems biology. J Immunol. 2023;210:888–94. https://doi.org/10.4049/jimmunol.2200610.

Article  CAS  PubMed  Google Scholar 

Bosticardo M, Notarangelo LD. Human thymus in health and disease: Recent advances in diagnosis and biology. Semin Immunol. 2023;66:101732. https://doi.org/10.1016/j.smim.2023.101732.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wei T, Zhang N, Guo Z, Chi F, Song Y, Zhu X. Wnt4 signaling is associated with the decrease of proliferation and increase of apoptosis during age-related thymic involution. Mol Med Rep. 2015;12:7568–76. https://doi.org/10.3892/mmr.2015.4343.

Article  CAS  PubMed  Google Scholar 

Han J, Zúñiga-Pflücker JC. High-oxygen submersion fetal thymus organ cultures enable FOXN1-dependent and -independent support of T lymphopoiesis. Front Immunol. 2021;12:652665. https://doi.org/10.3389/fimmu.2021.652665.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Srinivasan J, Vasudev A, Shasha C, Selden HJ, Perez E Jr, LaFleur B, Sinari SA, Krueger A, Richie ER, Ehrlich LI. The initial age-associated decline in early T-cell progenitors reflects fewer pre-thymic progenitors and altered signals in the bone marrow and thymus microenvironments. Aging Cell. 2023;22:e13870. https://doi.org/10.1111/acel.13870.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yin C, Pei XY, Shen H, Gao YN, Sun XY, Wang W, Ge Q, Zhang Y. Thymic homing of activated CD4+T cells induces degeneration of the thymic epithelium through excessive RANK signaling. Sci Rep. 2017;7:2421. https://doi.org/10.1038/s41598-017-02653-9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gui J, Mustachio LM, Su DM, Craig RW. Thymus size and age-related thymic involution: early programming, sexual dimorphism, progenitors and stroma. Aging Dis. 2012;3:280–90.

PubMed  PubMed Central  Google Scholar 

Itoh S, Ohno T, Kakizaki S, Ichinohasama R. Epstein-Barr virus-positive T-cell lymphoma cells having chromosome 22q11.2 deletion: an autopsy report of DiGeorge syndrome. Hum Pathol. 2011;42:2037–41. https://doi.org/10.1016/j.humpath.2010.03.014.

Article  CAS  PubMed  Google Scholar 

Chaudhry MS, Velardi E, Dudakov JA, van den Brink MR. Thymus: the next (re)generation. Immunol Rev. 2016;271:56–71. https://doi.org/10.1111/imr.12418.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tan J, Wang Y, Zhang N, Zhu X. Induction of epithelial to mesenchymal transition (EMT) and inhibition on adipogenesis: two different sides of the same coin? Feasible roles and mechanisms of transforming growth factor β1 (TGF-β1) in age-related thymic involution. Cell Biol Int. 2016;40:842–6. https://doi.org/10.1002/cbin.10625.

Article  CAS  PubMed  Google Scholar 

Ferrando-Martínez S, Ruiz-Mateos E, Dudakov JA, Velardi E, Grillari J, Kreil DP, Muñoz-Fernandez MÁ, van den Brink MR, Leal M. WNT signaling suppression in the senescent human thymus. J Gerontol A Biol Sci Med Sci. 2015;70:273–81. https://doi.org/10.1093/gerona/glu030.

Article  CAS  PubMed  Google Scholar 

Shultz LD, Goodwin N, Ishikawa F, Hosur V, Lyons BL, Greiner DL. Subcapsular transplantation of tissue in the kidney. Cold Spring Harb Protoc. 2014;2014:737–40. https://doi.org/10.1101/pdb.prot078089.

Article  PubMed  PubMed Central  Google Scholar 

De Vera MJ, Al-Harthi L, Gewurz AT. Assessing thymopoiesis in patients with common variable immunodeficiency as measured by T-cell receptor excision circles. Ann Allergy Asthma Immunol. 2004;93:478–84. https://doi.org/10.1016/S1081-1206(10)61416-0.

Article  PubMed  Google Scholar 

Machnes-Maayan D, Lev A, Katz U, Mishali D, Vardi A, Simon AJ, Somech R. Insight into normal thymic activity by assessment of peripheral blood samples. Immunol Res. 2015;61:198–205. https://doi.org/10.1007/s12026-014-8558-4.

Article  CAS  PubMed  Google Scholar 

Halouani A, Jmii H, Bodart G, Michaux H, Renard C, Martens H, Aouni M, Hober D, Geenen V, Jaïdane H. Assessment of thymic output dynamics after in utero infection of mice with Coxsackievirus B4. Front Immunol. 2020;11:481. https://doi.org/10.3389/fimmu.2020.00481.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hirano KI, Hosokawa H, Koizumi M, Endo Y, Yahata T, Ando K, Hozumi K. LMO2 is essential to maintain the ability of progenitors to differentiate into T-cell lineage in mice. Elife. 2021;10:e68227. https://doi.org/10.7554/eLife.68227.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen L, Xiao S, Manley NR. Foxn1 is required to maintain the postnatal thymic microenvironment in a dosage-sensitive manner. Blood. 2009;113:567–74. https://doi.org/10.1182/blood-2008-05-156265.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Guo J, Feng Y, Barnes P, Huang FF, Idell S, Su DM, Shams H. Deletion of FoxN1 in