Farley AM, Morris LX, Vroegindeweij E, Depreter ML, Vaidya H, Stenhouse FH, et al. Dynamics of thymus organogenesis and colonization in early human development. Development. 2013;140:2015–26. https://doi.org/10.1242/dev.087320.
Article
CAS
PubMed
PubMed Central
Google Scholar
Manley NR, Richie ER, Blackburn CC, Condie BG, Sage J. Structure and function of the thymic microenvironment. Front Biosci (Landmark Ed). 2011;16:2461–77. https://doi.org/10.2741/3866.
Article
CAS
Google Scholar
Guidos CJ. Synergy between the pre-T cell receptor and Notch: cementing the alphabeta lineage choice. J Exp Med. 2006;203:2233–7. https://doi.org/10.1084/jem.20060998.
Article
CAS
PubMed
PubMed Central
Google Scholar
Wang HX, Pan W, Zheng L, Zhong XP, Tan L, Liang Z, et al. Thymic epithelial cells contribute to thymopoiesis and T cell development. Front Immunol. 2019;10:3099. https://doi.org/10.3389/fimmu.2019.03099.
Article
CAS
PubMed
Google Scholar
Lynch HE, Goldberg GL, Chidgey A, Van den Brink MR, Boyd R, Sempowski GD. Thymic involution and immune reconstitution. Trends Immunol. 2009;30:366–73. https://doi.org/10.1016/j.it.2009.04.003.
Article
CAS
PubMed
PubMed Central
Google Scholar
Zhang W, Qu J, Liu GH, Belmonte JCI. The ageing epigenome and its rejuvenation. Nat Rev Mol Cell Biol. 2020;21:137–50. https://doi.org/10.1038/s41580-019-0204-5.
Article
CAS
PubMed
Google Scholar
Horvath S. DNA methylation age of human tissues and cell types. Genome Biol. 2013;14:R115. https://doi.org/10.1186/gb-2013-14-10-r115.
Article
PubMed
PubMed Central
Google Scholar
Schmidl C, Delacher M, Huehn J, Feuerer M. Epigenetic mechanisms regulating T-cell responses. J Allergy Clin Immunol. 2018;142:728–43. https://doi.org/10.1016/j.jaci.2018.07.014.
Article
CAS
PubMed
Google Scholar
Wu G, Hirabayashi K, Sato S, Akiyama N, Akiyama T, Shiota K, et al. DNA methylation profile of Aire-deficient mouse medullary thymic epithelial cells. BMC Immunol. 2012;13:58. https://doi.org/10.1186/1471-2172-13-58.
Article
CAS
PubMed
PubMed Central
Google Scholar
Reis MD, Csomos K, Dias LP, Prodan Z, Szerafin T, Savino W, et al. Decline of FOXN1 gene expression in human thymus correlates with age: possible epigenetic regulation. Immun Ageing. 2015;12:18. https://doi.org/10.1186/s12979-015-0045-9.
Article
CAS
PubMed
PubMed Central
Google Scholar
Celona B, Weiner A, Di Felice F, Mancuso FM, Cesarini E, Rossi RL, et al. Substantial histone reduction modulates genomewide nucleosomal occupancy and global transcriptional output. PLoS Biol. 2011;9: e1001086. https://doi.org/10.1371/journal.pbio.1001086.
Article
CAS
PubMed
PubMed Central
Google Scholar
Jambhekar A, Dhall A, Shi Y. Roles and regulation of histone methylation in animal development. Nat Rev Mol Cell Biol. 2019;20:625–41. https://doi.org/10.1038/s41580-019-0151-1.
Article
CAS
PubMed
PubMed Central
Google Scholar
Barthlott T, Handel AE, Teh HY, Wirasinha RC, Hafen K, Zuklys S, et al. Indispensable epigenetic control of thymic epithelial cell development and function by polycomb repressive complex 2. Nat Commun. 2021;12:3933. https://doi.org/10.1038/s41467-021-24158-w.
Article
CAS
PubMed
PubMed Central
Google Scholar
Zhang W, Li J, Suzuki K, Qu J, Wang P, Zhou J, et al. Aging stem cells. A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging. Science. 2015;348:1160–3. https://doi.org/10.1126/science.aaa1356.
Article
CAS
PubMed
PubMed Central
Google Scholar
Keenan CR, Iannarella N, Naselli G, Bediaga NG, Johanson TM, Harrison LC, et al. Extreme disruption of heterochromatin is required for accelerated hematopoietic aging. Blood. 2020;135:2049–58. https://doi.org/10.1182/blood.2019002990.
Article
PubMed
Google Scholar
Bleul CC, Corbeaux T, Reuter A, Fisch P, Monting JS, Boehm T. Formation of a functional thymus initiated by a postnatal epithelial progenitor cell. Nature. 2006;441:992–6. https://doi.org/10.1038/nature04850.
Article
CAS
PubMed
Google Scholar
Alves NL, Takahama Y, Ohigashi I, Ribeiro AR, Baik S, Anderson G, et al. Serial progression of cortical and medullary thymic epithelial microenvironments. Eur J Immunol. 2014;44:16–22. https://doi.org/10.1002/eji.201344110.
Article
CAS
PubMed
Google Scholar
Takahama Y, Ohigashi I, Baik S, Anderson G. Generation of diversity in thymic epithelial cells. Nat Rev Immunol. 2017;17:295–305. https://doi.org/10.1038/nri.2017.12.
Article
CAS
PubMed
Google Scholar
Abramson J, Anderson G. Thymic epithelial cells. Annu Rev Immunol. 2017;35:85–118. https://doi.org/10.1146/annurev-immunol-051116-052320.
Article
CAS
PubMed
Google Scholar
Liu D, Kousa AI, O’Neill KE, Rouse P, Popis M, Farley AM, et al. Canonical Notch signaling controls the early thymic epithelial progenitor cell state and emergence of the medullary epithelial lineage in fetal thymus development. Development (Cambridge, England). 2020;147:178582. https://doi.org/10.1242/dev.178582.
Article
CAS
Google Scholar
Li J, Gordon J, Chen ELY, Xiao S, Wu L, Zúñiga-Pflücker JC, et al. NOTCH1 signaling establishes the medullary thymic epithelial cell progenitor pool during mouse fetal development. Development (Cambridge, England). 2020;147:178988. https://doi.org/10.1242/dev.178988.
Article
CAS
Google Scholar
Boehm T, Scheu S, Pfeffer K, Bleul CC. Thymic medullary epithelial cell differentiation, thymocyte emigration, and the control of autoimmunity require lympho-epithelial cross talk via LTbetaR. J Exp Med. 2003;198:757–69. https://doi.org/10.1084/jem.20030794.
Article
CAS
PubMed
PubMed Central
Google Scholar
Rossi SW, Kim MY, Leibbrandt A, Parnell SM, Jenkinson WE, Glanville SH, et al. RANK signals from CD4+3- inducer cells regulate development of Aire-expressing epithelial cells in the thymic medulla. J Exp Med. 2007;204:1267–72. https://doi.org/10.1084/jem.20062497.
Article
CAS
PubMed
PubMed Central
Google Scholar
Akiyama T, Shimo Y, Yanai H, Qin J, Ohshima D, Maruyama Y, et al. The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance. Immunity. 2008;29:423–37. https://doi.org/10.1016/j.immuni.2008.06.015.
Article
CAS
PubMed
Google Scholar
Hikosaka Y, Nitta T, Ohigashi I, Yano K, Ishimaru N, Hayashi Y, et al. The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator. Immunity. 2008;29:438–50. https://doi.org/10.1016/j.immuni.2008.06.018.
Article
CAS
PubMed
Google Scholar
White AJ, Nakamura K, Jenkinson WE, Saini M, Sinclair C, Seddon B, et al. Lymphotoxin signals from positively selected thymocytes regulate the terminal differentiation of medullary thymic epithelial cells. J Immunol. 2010;185:4769–76. https://doi.org/10.4049/jimmunol.1002151.
Article
CAS
PubMed
Google Scholar
Liang Z, Zhang L, Su H, Luan R, Na N, Sun L, et al. MTOR signaling is essential for the development of thymic epithelial cells and the induction of central immune tolerance. Autophagy. 2018;14:505–17. https://doi.org/10.1080/15548627.2017.1376161.
Article
CAS
PubMed
PubMed Central
Google Scholar
Liang Z, Zhang Q, Dong X, Zhang Z, Wang H, Zhang J, et al. mTORC2 negatively controls the maturation process of medullary thymic epithelial cells by inhibiting the LTbetaR/RANK-NF-kappaB axis. J Cell Physiol. 2020. https://doi.org/10.1002/jcp.30192.
Article
PubMed
PubMed Central
Google Scholar
Balciunaite G, Keller MP, Balciunaite E, Piali L, Zuklys S, Mathieu YD, et al. Wnt glycoproteins regulate the expression of FoxN1, the gene defective in nude mice. Nat Immunol. 2002;3:1102–8. https://doi.org/10.1038/ni850.
Article
CAS
PubMed
Google Scholar
Goldfarb Y, Kadouri N, Levi B, Sela A, Herzig Y, Cohen RN, et al. HDAC3 is a master regulator of mTEC development. Cell Rep. 2016;15:651–65. https://doi.org/10.1016/j.celrep.2016.03.048.
Article
CAS
PubMed
PubMed Central
Google Scholar
Zhang Q, Liang Z, Zhang J, Lei T, Dong X, Su H, et al. Sirt6 regulates the development of medullary thymic epithelial cells and contributes to the establishment of central immune tolerance. Front Cell Dev Biol. 2021;9: 655552. https://doi.org/10.3389/fcell.2021.655552.
Article
PubMed
PubMed Central
Google Scholar
Metzger TC, Khan IS, Gardner JM, Mouchess ML, Johannes KP, Krawisz AK, et al. Lineage tracing and cell ablation identify a post-aire-expressing thymic epithelial cell population. Cell Rep. 2013;5:166–79. https://doi.org/10.1016/j.celrep.2013.08.038.
Article
CAS
PubMed
Google Scholar
Corbeaux T, Hess I, Swann JB, Kanzler B, Haas-Assenbaum A, Boehm T. Thymopoiesis in mice depends on a Foxn1-positive thymic epithelial cell lineage. Proc Natl Acad Sci U S A. 2010;107:16613–8. https://doi.org/10.1073/pnas.1004623107.
Article
PubMed
PubMed Central
Google Scholar
Tsai PT, Lee RA, Wu H. BMP4 acts upstream of FGF in modulating thymic stroma and regulating thymopoiesis. Blood. 2003;102:3947–53. https://doi.org/10.1182/blood-2003-05-1657.
Article
CAS
PubMed
Google Scholar
Barsanti M, Lim JM, Hun ML, Lister N, Wong K, Hammett MV, et al. A novel Foxn1(eGFP/+) mouse model identifies Bmp4-induced maintenance of Foxn1 expression and thymic epithelial progenitor populations. Eur J Immunol. 2017;47:291–304. https://doi.org/10.1002/eji.201646553.
Article
CAS
PubMed
Google Scholar
Zhou L, Seo K, Wong H, Mi Q. MicroRNAs and immune regulatory T cells. Int Immunopharmacol. 2009;9:524–7. https://doi.org/10.1016/j.intimp.2009.01.017.
Article
CAS
PubMed
Google Scholar
Zuklys S, Mayer CE, Zhanybekova S, Stefanski HE, Nusspaumer G, Gill J, et al. MicroRNAs control the maintenance of thymic epithelia and their competence for T lineage commitment and thymocyte selection. J Immunol. 2012;189:3894–904. https://doi.org/10.4049/jimmunol.1200783.
Article
CAS
PubMed
Google Scholar
Cotrim-Sousa L, Freire-Assis A, Pezzi N, Tanaka P, Oliveira E, Passos G. Adhesion between medullary thymic epithelial cells and thymocytes is regulated by miR-181b-5p and miR-30b. Mol Immunol. 2019;114:600–11. https://doi.org/10.1016/j.molimm.2019.09.010.
Article
CAS
PubMed
Google Scholar
Chen P, Zhang H, Sun X, Hu Y, Jiang W, Liu Z, et al. microRNA-449a modulates medullary thymic epithelial cell differentiation. Sci Rep. 2017;7:15915. https://doi.org/10.1038/s41598-017-16162-2.
Article
CAS
PubMed
PubMed Central
Google Scholar
Pangrazzi L, Weinberger B. T cells, aging and senescence. Exp Gerontol. 2020;134:110887. https://doi.org/10.1016/j.exger.2020.110887.
Article
CAS
PubMed
Google Scholar
Ansari AR, Liu H. Acute thymic involution and mechanisms for recovery. Arch Immunol Ther Exp (Warsz). 2017;65:401–20. https://doi.org/10.1007/s00005-017-0462-x.
Article
CAS
Google Scholar
Lins MP, Smaniotto S. Potential impact of SARS-CoV-2 infection on the thymus. Can J Microbiol. 2021;67:23–8. https://doi.org/10.1139/cjm-2020-0170.
Article
CAS
PubMed
Google Scholar
de Meis J, Savino W. Mature peripheral T cells are important to preserve thymus function and selection of thymocytes during Mycobacterium tuberculosis infection. Immunotherapy. 2013;5:573–6. https://doi.org/10.2217/imt.13.41.
Article
CAS
PubMed
Google Scholar
Mucci J, Hidalgo A, Mocetti E, Argibay PF, Leguizamon MS, Campetella O. Thymocyte depletion in Trypanosoma cruzi infection is mediated by trans-sialidase-induced apoptosis on nurse cells complex. Proc Natl Acad Sci U S A. 2002;99:3896–901. https://doi.org/10.1073/pnas.052496399.
Article
CAS
PubMed
PubMed Central
Google Scholar
Mendes-Giannini MJ, Monteiro da Silva JL, de Fatima da Silva J, Donofrio FC, Miranda ET, Andreotti PF, et al. Interactions of Paracoccidioides brasiliensis with host cells: recent advances. Mycopathologia. 2008;165:237–48. https://doi.org/10.1007/s11046-007-9074-z.
Article
PubMed
Google Scholar
Billard M, Gruver A, Sempowski G. Acute endotoxin-induced thymic atrophy is characterized by intrathymic inflammatory and wound healing responses. PLoS ONE. 2011;6: e17940. https://doi.org/10.1371/journal.pone.0017940.
Article
CAS
PubMed
PubMed Central
Google Scholar
DeBo RJ, Register TC, Caudell DL, Sempowski GD, Dugan G, Gray S, et al. Molecular and cellular profiling of acute responses to total body radiation exposure in ovariectomized female cynomolgus macaques. Int J Radiat Biol. 2015;91:510–8. https://doi.org/10.3109/09553002.2015.1028597.
Article
CAS
PubMed
PubMed Central
Google Scholar
Taves MD, Ashwell JD. Glucocorticoids in T cell development, differentiation and function. Nat Rev Immunol. 2021;21:233–43. https://doi.org/10.1038/s41577-020-00464-0.
Article
CAS
PubMed
Google Scholar
Cepeda S, Griffith AV. Thymic stromal cells: roles in atrophy and age-associated dysfunction of the thymus. Exp Gerontol. 2018;105:113–7. https://doi.org/10.1016/j.exger.2017.12.022.
Article
CAS
PubMed
Google Scholar
Huang HB, Xiang QH, Wu H, Ansari AR, Wen L, Ge XH, et al. TLR4 is constitutively expressed in chick thymic epithelial cells. Vet Immunol Immunopathol. 2014;158:182–8. https://doi.org/10.1016/j.vetimm.2014.01.005.
Article
CAS
PubMed
Google Scholar
Fafian-Labora JA, O’Loghlen A. Classical and nonclassical intercellular communication in senescence and ageing. Trends Cell Biol. 2020;30:628–39. https://doi.org/10.1016/j.tcb.2020.05.003.
Article
PubMed
Google Scholar
Shanley D, Aw D, Manley N, Palmer D. An evolutionary perspective on the mechanisms of immunosenescence. Trends Immunol. 2009;30:374–81. https://doi.org/10.1016/j.it.2009.05.001.
Article
CAS
PubMed
Google Scholar
Wu H, Qin X, Dai H, Zhang Y. Time-course transcriptome analysis of medullary thymic epithelial cells in the early phase of thymic involution. Mol Immunol. 2018;99:87–94. https://doi.org/10.1016/j.molimm.2018.04.010.
Article
CAS
PubMed
Google Scholar
Yin C, Pei XY, Shen H, Gao YN, Sun XY, Wang W, et al. 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
Hale LP, Markert ML. Corticosteroids regulate epithelial cell differentiation and Hassall body formation in the human thymus. J Immunol. 2004;172:617–24. https://doi.org/10.4049/jimmunol.172.1.617.
Article
CAS
PubMed
Google Scholar
Foster AD, Sivarapatna A, Gress RE. The aging immune system and its relationship with cancer. Aging health. 2011;7:707–18. https://doi.org/10.2217/ahe.11.56.
Article
CAS
PubMed
PubMed Central
Google Scholar
Cicin-Sain L, Smyk-Pearson S, Currier N, Byrd L, Koudelka C, Robinson T, et al. Loss of naive T cells and repertoire constriction predict poor response to vaccination in old primates. J Immunol. 2010;184:6739–45. https://doi.org/10.4049/jimmunol.0904193.
Article
CAS
PubMed
Google Scholar
Boraschi D, Italiani P. Immunosenescence and vaccine failure in the elderly: strategies for improving response. Immunol Lett. 2014;162:346–53. https://doi.org/10.1016/j.imlet.2014.06.006.
Article
CAS
PubMed
Google Scholar
Pera A, Campos C, Lopez N, Hassouneh F, Alonso C, Tarazona R, et al. Immunosenescence: implications for response to infection and vaccination in older people. Maturitas. 2015;82:50–5. https://doi.org/10.1016/j.maturitas.2015.05.004.
Article
CAS
PubMed
Google Scholar
Prelog M. Aging of the immune system: a risk factor for autoimmunity? Autoimmun Rev. 2006;5:136–9. https://doi.org/10.1016/j.autrev.2005.09.008.
Article
CAS
PubMed
Google Scholar
Di Micco R, Krizhanovsky V, Baker D, d’Adda di Fagagna F. Cellular senescence in ageing: from mechanisms to therapeutic opportunities. Nat Rev Mol Cell Biol. 2021;22:75–95. https://doi.org/10.1038/s41580-020-00314-w.
Article
CAS
PubMed
Google Scholar
Salminen A, Kaarniranta K, Hiltunen M, Kauppinen A. Histone demethylase Jumonji D3 (JMJD3/KDM6B) at the nexus of epigenetic regulation of inflammation and the aging process. J Mol Med (Berl). 2014;92:1035–43. https://doi.org/10.1007/s00109-014-1182-x.
Article
CAS
Google Scholar
De Santa F, Totaro MG, Prosperini E, Notarbartolo S, Testa G, Natoli G. The histone H3 lysine-27 demethylase Jmjd3 links inflammation to inhibition of polycomb-mediated gene silencing. Cell. 2007;130:1083–94. https://doi.org/10.1016/j.cell.2007.08.019.
Article
CAS
PubMed
Google Scholar
Liu Z, Zhang H, Hu Y, Liu D, Li L, Li C, et al. Critical role of histone H3 lysine 27 demethylase Kdm6b in the homeostasis and function of medullary thymic epithelial cells. Cell Death Differ. 2020;27:2843–55. https://doi.org/10.1038/s41418-020-0546-8.
Article
CAS
PubMed
PubMed Central
Google Scholar
Bertonha FB, Bando SY, Ferreira LR, Chaccur P, Vinhas C, Zerbini MCN, et al. Age-related transcriptional modules and TF-miRNA-mRNA interactions in neonatal and infant human thymus. PLoS ONE. 2020;15: e0227547. https://doi.org/10.1371/journal.pone.0227547.
Article
CAS
PubMed
PubMed Central
Google Scholar
Xu M, Gan T, Ning H, Wang L. MicroRNA functions in thymic biology: thymic development and involution. Front Immunol. 2018;9:2063. https://doi.org/10.3389/fimmu.2018.02063.
Article
CAS
PubMed
PubMed Central
Google Scholar
Jia H-L, Zeng X-Q, Huang F, Liu Y-M, Gong B-S, Zhang K-Z, et al. Integrated microRNA and mRNA sequencing analysis of age-related changes to mouse thymic epithelial cells. IUBMB Life. 2018;70:678–90. https://doi.org/10.1002/iub.1864.
Article
CAS
PubMed
Google Scholar
Park CY, Jeker LT, Carver-Moore K, Oh A, Liu HJ, Cameron R, et al. A resource for the conditional ablation of microRNAs in the mouse. Cell Rep. 2012;1:385–91. https://doi.org/10.1016/j.celrep.2012.02.008.
Article
CAS
PubMed
PubMed Central
Google Scholar
Khan IS, Park CY, Mavropoulos A, Shariat N, Pollack JL, Barczak AJ, et al. Identification of MiR-205 as a MicroRNA that is highly expressed in medullary thymic epithelial cells. PLoS ONE. 2015;10: e0135440. https://doi.org/10.1371/journal.pone.0135440.
Article
CAS
PubMed
PubMed Central
Google Scholar
Gong B, Wang X, Li B, Li Y, Lu R, Zhang K, et al. miR-205-5p inhibits thymic epithelial cell proliferation via FA2H-TFAP2A feedback regulation in age-associated thymus involution. Mol Immunol. 2020;122:173–85. https://doi.org/10.1016/j.molimm.2020.04.011.
Article
CAS
PubMed
Google Scholar
Wang X, Li Y, Gong B, Zhang K, Ma Y, Li Y. miR-199b-5p enhances the proliferation of medullary thymic epithelial cells via regulating Wnt signaling by targeting Fzd6. Acta Biochim Biophys Sin (Shanghai). 2021;53:36–45. https://doi.org/10.1093/abbs/gmaa145.
Article
CAS
Google Scholar
Hirayama T, Asano Y, Iida H, Watanabe T, Nakamura T, Goitsuka R. Meis1 is required for the maintenance of postnatal thymic epithelial cells. PLoS ONE. 2014;9: e89885. https://doi.org/10.1371/journal.pone.0089885.
Article
CAS
PubMed
PubMed Central
Google Scholar
Guo Z, Chi F, Song Y, Wang C, Yu R, Wei T, et al. Transcriptome analysis of murine thymic epithelial cells reveals age-associated changes in microRNA expression. Int J Mol Med. 2013;32:835–42. https://doi.org/10.3892/ijmm.2013.1471.
Article
CAS
PubMed
Google Scholar
Mashima R. Physiological roles of miR-155. Immunology. 2015;145:323–33. https://doi.org/10.1111/imm.12468.
Article
CAS
PubMed
PubMed Central
Google Scholar
Dong J, Warner LM, Lin LL, Chen MC, O’Connell RM, Lu LF. miR-155 promotes T reg cell development by safeguarding medullary thymic epithelial cell maturation. J Exp Med. 2021;218: e20192423. https://doi.org/10.1084/jem.20192423.
Article
CAS
PubMed
Google Scholar
Taganov KD, Boldin MP, Chang KJ, Baltimore D. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A. 2006;103:12481–6. https://doi.org/10.1073/pnas.0605298103.
Article
CAS
PubMed
PubMed Central
Google Scholar
Du H, Wang Y, Liu X, Wang S, Wu S, Yuan Z, et al. miRNA-146a-5p mitigates stress-induced premature senescence of D-galactose-induced primary thymic stromal cells. Cytokine. 2020;137: 155314. https://doi.org/10.1016/j.cyto.2020.155314.
Article
CAS
PubMed
Google Scholar
Guo D, Ye Y, Qi J, Xu L, Zhang L, Tan X, et al. MicroRNA-195a-5p inhibits mouse medullary thymic epithelial cells proliferation by directly targeting Smad7. Acta Biochim Biophys Sin. 2016;48:290–7. https://doi.org/10.1093/abbs/gmv136.
Article
CAS
PubMed
PubMed Central
Google Scholar
Kuchen S, Resch W, Yamane A, Kuo N, Li Z, Chakraborty T, et al. Regulation of microRNA expression and abundance during lymphopoiesis. Immunity. 2010;32:828–39. https://doi.org/10.1016/j.immuni.2010.05.009.
Article
CAS
PubMed
PubMed Central
Google Scholar
Guo D, Ye Y, Qi J, Zhang L, Xu L, Tan X, et al. MicroRNA-181a-5p enhances cell proliferation in medullary thymic epithelial cells via regulating TGF-beta signaling. Acta Biochim Biophys Sin. 2016;48:840–9. https://doi.org/10.1093/abbs/gmw068.
Article
CAS
PubMed
Google Scholar
Stefanski HE, Xing Y, Taylor PA, Maio S, Henao-Meija J, Williams A, et al. Despite high levels of expression in thymic epithelial cells, miR-181a1 and miR-181b1 are not required for thymic development. PLoS ONE. 2018;13: e0198871. https://doi.org/10.1371/journal.pone.0198871.
Article
CAS
PubMed
PubMed Central
Google Scholar
Li W, Ma N, Yuwen T, Yu B, Zhou Y, Yao Y, et al. Comprehensive analysis of circRNA expression profiles and circRNA-associated competing endogenous RNA networks in the development of mouse thymus. J Cell Mol Med. 2020;24:6340–9. https://doi.org/10.1111/jcmm.15276.
Article
CAS
PubMed
PubMed Central
Google Scholar
Messias CV, Loss-Morais G, Carvalho JB, Gonzalez MN, Cunha DP, Vasconcelos Z, et al. Zika virus targets the human thymic epithelium. Sci Rep. 2020;10:1378. https://doi.org/10.1038/s41598-020-58135-y.
Article
CAS
PubMed
PubMed Central
Google Scholar
Wei C, Guo D, Li Y, Zhang K, Liang G, Li Y, et al. Profiling analysis of 17β-estradiol-regulated lncRNAs in mouse thymic epithelial cells. Physiol Genom. 2018;50:553–62. https://doi.org/10.1152/physiolgenomics.00098.2017.
Article
CAS
Google Scholar
Li B, Zhang K, Ye Y, Xing J, Wu Y, Ma Y, et al. Effects of castration on miRNA, lncRNA, and mRNA profiles in mice thymus. Genes (Basel). 2020. https://doi.org/10.3390/genes11020147.
Article
PubMed
PubMed Central
Google Scholar
O’Neill KE, Bredenkamp N, Tischner C, Vaidya HJ, Stenhouse FH, Peddie CD, et al. Foxn1 Is dynamically regulated in thymic epithelial cells during embryogenesis and at the onset of thymic involution. PLoS ONE. 2016;11: e0151666. https://doi.org/10.1371/journal.pone.0151666.
Article
CAS
PubMed
PubMed Central
Google Scholar
Zook EC, Krishack PA, Zhang S, Zeleznik-Le NJ, Firulli AB, Witte PL, et al. Overexpression of Foxn1 attenuates age-associated thymic involution and prevents the expansion of peripheral CD4 memory T cells. Blood. 2011;118:5723–31. https://doi.org/10.1182/blood-2011-03-342097.
Article
CAS
PubMed
PubMed Central
Google Scholar
Larsen BM, Cowan JE, Wang Y, Tanaka Y, Zhao Y, Voisin B, et al. Identification of an intronic regulatory element necessary for tissue-specific expression of Foxn1 in thymic epithelial cells. J Immunol. 2019;203:686–95. https://doi.org/10.4049/jimmunol.1801540.
Article
CAS
PubMed
Google Scholar
Xu M, Sizova O, Wang L, Su DM. A fine-tune role of mir-125a-5p on foxn1 during age-associated changes in the thymus. Aging Dis. 2017;8:277–86. https://doi.org/10.14336/ad.2016.1109.
Article
PubMed
PubMed Central
Google Scholar
Yuan S, Li F, Meng Q, Zhao Y, Chen L, Zhang H, et al. Post-transcriptional regulation of keratinocyte progenitor cell expansion, differentiation and hair follicle regression by miR-22. PLoS Genet. 2015;11: e1005253. https://doi.org/10.1371/journal.pgen.1005253.
Article
CAS
PubMed
PubMed Central
Google Scholar
Hoover AR, Dozmorov I, MacLeod J, Du Q, de la Morena MT, Forbess J, et al. MicroRNA-205 maintains T cell development following stress by regulating Forkhead Box N1 and selected chemokines. J Biol Chem. 2016;291:23237–47. https://doi.org/10.1074/jbc.M116.744508.
Article
CAS
PubMed
PubMed Central
Google Scholar
Newman J, Aitkenhead H, Gavard A, Rota I, Handel A, Hollander G, et al. The crystal structure of human forkhead box N1 in complex with DNA reveals the structural basis for forkhead box family specificity. J Biol Chem. 2020;295:2948–58. https://doi.org/10.1074/jbc.RA119.010365.
Article
CAS
PubMed
Google Scholar
Du Q, Huynh L, Coskun F, Molina E, King M, Raj P, et al. FOXN1 compound heterozygous mutations cause selective thymic hypoplasia in humans. J Clin Investig. 2019;129:4724–38. https://doi.org/10.1172/jci127565.
Article
CAS
PubMed
PubMed Central
Google Scholar
Schuddekopf K, Schorpp M, Boehm T. The whn transcription factor encoded by the nude locus contains an evolutionarily conserved and functionally indispensable activation domain. Proc Natl Acad Sci U S A. 1996;93:9661–4. https://doi.org/10.1073/pnas.93.18.9661.
Article
CAS
PubMed
PubMed Central
Google Scholar
Liu B, Liu YF, Du YR, Mardaryev AN, Yang W, Chen H, et al. Cbx4 regulates the proliferation of thymic epithelial cells and thymus function. Development. 2013;140:780–8. https://doi.org/10.1242/dev.085035.
Article
CAS
PubMed
PubMed Central
Google Scholar
Cohen I, Ezhkova E. Cbx4: a new guardian of p63’s domain of epidermal control. J Cell Biol. 2016;212:9–11. https://doi.org/10.1083/jcb.201512032.
Article
CAS
PubMed
PubMed Central
Google Scholar
Ren X, Hu B, Song M, Ding Z, Dang Y, Liu Z, et al. Maintenance of nucleolar homeostasis by CBX4 alleviates senescence and osteoarthritis. Cell Rep. 2019;26:3643–56. https://doi.org/10.1016/j.celrep.2019.02.088.
Article
CAS
PubMed
Google Scholar
Singarapu N, Ma K, Reeh KAG, Shen J, Lancaster JN, Yi S, et al. Polycomb repressive complex 2 is essential for development and maintenance of a functional TEC compartment. Sci Rep. 2018;8:14335. https://doi.org/10.1038/s41598-018-32729-z.
Article
CAS
PubMed
PubMed Central
Google Scholar
Burnley P, Rahman M, Wang H, Zhang Z, Sun X, Zhuge Q, et al. Role of the p63-FoxN1 regulatory axis in thymic epithelial cell homeostasis during aging. Cell Death Dis. 2013;4:10. https://doi.org/10.1038/cddis.2013.460.
Article
CAS
Google Scholar
Ansar K, Yasin A, Bahman Y. Multiple functions of p21 in cell cycle, apoptosis and transcriptional regulation after DNA damage. DNA Repair. 2016;42:63–71. https://doi.org/10.1016/j.dnarep.2016.04.008.
Article
CAS
Google Scholar
Gerasymchuk M, Cherkasova V, Kovalchuk O, Kovalchuk I. The role of microRNAs in organismal and skin aging. Int J Mol Sci. 2020;21:5281. https://doi.org/10.3390/ijms21155281.
Article
CAS
PubMed Central
Google Scholar
Xu M, Zhang X, Hong R, Su D, Wang L. MicroRNAs regulate thymic epithelium in age-related thymic involution via down- or upregulation of transcription factors. J Immunol Res. 2017;2017:2528957. https://doi.org/10.1155/2017/2528957.
Article
CAS
PubMed
PubMed Central
Google Scholar
De Cola A, Volpe S, Budani MC, Ferracin M, Lattanzio R, Turdo A, et al. miR-205-5p-mediated downregulation of ErbB/HER receptors in breast cancer stem cells results in targeted therapy resistance. Cell Death Dis. 2015;6: e1823. https://doi.org/10.1038/cddis.2015.192.
Article
CAS
PubMed
PubMed Central
Google Scholar
Tilg H, Moschen AR. Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol. 2006;6:772–83. https://doi.org/10.1038/nri1937.
Article
CAS
PubMed
Google Scholar
Tang W, Zeve D, Suh JM, Bosnakovski D, Kyba M, Hammer RE, et al. White fat progenitor cells reside in the adipose vasculature. Science. 2008;322:583–6. https://doi.org/10.1126/science.1156232.
Article
CAS
PubMed
PubMed Central
Google Scholar
Dixit VD. Thymic fatness and approaches to enhance thymopoietic fitness in aging. Curr Opin Immunol. 2010;22:521–8. https://doi.org/10.1016/j.coi.2010.06.010.
Article
CAS
PubMed
PubMed Central
Google Scholar
Rezzani R, Nardo L, Favero G, Peroni M, Rodella LF. Thymus and aging: morphological, radiological, and functional overview. Age (Dordr). 2014;36:313–51. https://doi.org/10.1007/s11357-013-9564-5.
Article
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
Hauri-Hohl MM, Zuklys S, Keller MP, Jeker LT, Barthlott T, Moon AM, et al. TGF-beta signaling in thymic epithelial cells regulates thymic involution and postirradiation reconstitution. Blood. 2008;112:626–34. https://doi.org/10.1182/blood-2007-10-115618.
Article
CAS
PubMed
PubMed Central
Google Scholar
Chen R, Wang K, Feng Z, Zhang MY, Wu J, Geng JJ, et al. CD147 deficiency in T cells prevents thymic involution by inhibiting the EMT process in TECs in the presence of TGFβ. Cell Mol Immunol. 2020. https://doi.org/10.1038/s41423-019-0353-7.
Article
PubMed
PubMed Central
Google Scholar
Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 2008;10:593–601. https://doi.org/10.1038/ncb1722.
Article
CAS
PubMed
Google Scholar
Kvell K, Varecza Z, Bartis D, Hesse S, Parnell S, Anderson G, et al. Wnt4 and LAP2alpha as pacemakers of thymic epithelial senescence. PLoS ONE. 2010;5: e10701. https://doi.org/10.1371/journal.pone.0010701.
Article
CAS
PubMed
PubMed Central
Google Scholar
Chen X, Luo Y, Jia G, Liu G, Zhao H, Huang Z. FTO promotes adipogenesis through inhibition of the Wnt/beta-catenin signaling pathway in porcine intramuscular preadipocytes. Anim Biotechnol. 2017;28:268–74. https://doi.org/10.1080/10495398.2016.1273835.
Article
CAS
PubMed
Google Scholar
Jeon M, Rahman N, Kim YS. Wnt/beta-catenin signaling plays a distinct role in methyl gallate-mediated inhibition of adipogenesis. Biochem Biophys Res Commun. 2016;479:22–7. https://doi.org/10.1016/j.bbrc.2016.08.178.
Article
CAS
PubMed
Google Scholar
Ross SE, Hemati N, Longo KA, Bennett CN, Lucas PC, Erickson RL, et al. Inhibition of adipogenesis by Wnt signaling. Science. 2000;289:950–3. https://doi.org/10.1126/science.289.5481.950.
Article
CAS
PubMed
Google Scholar
Weerkamp F, Baert MR, Naber BA, Koster EE, de Haas EF, Atkuri KR, et al. Wnt signaling in the thymus is regulated by differential expression of intracellular signaling molecules. Proc Natl Acad Sci U S A. 2006;103:3322–6. https://doi.org/10.1073/pnas.0511299103.
Article
CAS
PubMed
PubMed Central
Google Scholar
Ferrando-Martinez S, Ruiz-Mateos E, Dudakov JA, Velardi E, Grillari J, Kreil DP, et al. WNT signaling suppression in the senescent human thymus. J Gerontol Ser Biol Sci Med Sci. 2015;70:273–81. https://doi.org/10.1093/gerona/glu030.
Article
CAS
Google Scholar
Hu T, Phiwpan K, Guo J, Zhang W, Guo J, Zhang Z, et al. MicroRNA-142-3p negatively regulates canonical Wnt signaling pathway. PLoS ONE. 2016;11: e0158432. https://doi.org/10.1371/journal.pone.0158432.
Article
CAS
PubMed
PubMed Central
Google Scholar
Karbiener M, Fischer C, Nowitsch S, Opriessnig P, Papak C, Ailhaud G, et al. microRNA miR-27b impairs human adipocyte differentiation and targets PPARgamma. Biochem Biophys Res Commun. 2009;390:247–51. https://doi.org/10.1016/j.bbrc.2009.09.098.
Article
CAS
PubMed
Google Scholar
Jennewein C, von Knethen A, Schmid T, Brune B. MicroRNA-27b contributes to lipopolysaccharide-mediated peroxisome proliferator-activated receptor gamma (PPARgamma) mRNA destabilization. J Biol Chem. 2010;285:11846–53. https://doi.org/10.1074/jbc.M109.066399.
Article
CAS
PubMed
PubMed Central
Google Scholar
Sun L, Trajkovski M. MiR-27 orchestrates the transcriptional regulation of brown adipogenesis. Metabolism. 2014;63:272–82. https://doi.org/10.1016/j.metabol.2013.10.004.
Article
CAS
PubMed
Google Scholar
Chen SZ, Xu X, Ning LF, Jiang WY, Xing C, Tang QQ, et al. miR-27 impairs the adipogenic lineage commitment via targeting lysyl oxidase. Obesity (Silver Spring). 2015;23:2445–53. https://doi.org/10.1002/oby.21319.
Article
CAS
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
Talaber G, Kvell K, Varecza Z, Boldizsar F, Parnell SM, Jenkinson EJ, et al. Wnt-4 protects thymic epithelial cells against dexamethasone-induced senescence. Rejuvenation Res. 2011;14:241–8. https://doi.org/10.1089/rej.2010.1110.
Article
CAS
PubMed
PubMed Central
Google Scholar
Zuklys S, Gill J, Keller MP, Hauri-Hohl M, Zhanybekova S, Balciunaite G, et al. Stabilized β-catenin in thymic epithelial cells blocks thymus development and function. J Immunol. 2009;182:2997–3007. https://doi.org/10.4049/jimmunol.0713723.
Article
CAS
PubMed
Google Scholar
Ramadoss S, Chen X, Wang CY. Histone demethylase KDM6B promotes epithelial-mesenchymal transition. J Biol Chem. 2012;287:44508–17. https://doi.org/10.1074/jbc.M112.424903.
Article
CAS
PubMed
PubMed Central
Google Scholar
Griffith AV, Fallahi M, Venables T, Petrie HT. Persistent degenerative changes in thymic organ function revealed by an inducible model of organ regrowth. Aging Cell. 2012;11:169–77. https://doi.org/10.1111/j.1474-9726.2011.00773.x.
Article
CAS
PubMed
Google Scholar
Koh AS, Miller EL, Buenrostro JD, Moskowitz DM, Wang J, Greenleaf WJ, et al. Rapid chromatin repression by Aire provides precise control of immune tolerance. Nat Immunol. 2018;19:162–72. https://doi.org/10.1038/s41590-017-0032-8.
Article
CAS
PubMed
PubMed Central
Google Scholar
Sansom SN, Shikama-Dorn N, Zhanybekova S, Nusspaumer G, Macaulay IC, Deadman ME, et al. Population and single-cell genomics reveal the Aire dependency, relief from Polycomb silencing, and distribution of self-antigen expression in thymic epithelia. Genome Res. 2014;24:1918–31. https://doi.org/10.1101/gr.171645.113.
Article
CAS
PubMed
PubMed Central
Google Scholar
Handel AE, Shikama-Dorn N, Zhanybekova S, Maio S, Graedel AN, Zuklys S, et al. Comprehensively profiling the chromatin architecture of tissue restricted antigen expression in thymic epithelial cells over development. Front Immunol. 2018;9:2120. https://doi.org/10.3389/fimmu.2018.02120.
Article
CAS
PubMed
PubMed Central
Google Scholar
Perniola R. Twenty years of AIRE. Front Immunol. 2018;9:98. https://doi.org/10.3389/fimmu.2018.00098.
Article
CAS
PubMed
PubMed Central
Google Scholar
Incani F, Serra M, Meloni A, Cossu C, Saba L, Cabras T, et al. AIRE acetylation and deacetylation: effect on protein stability and transactivation activity. J Biomed Sci. 2014;21:85. https://doi.org/10.1186/s12929-014-0085-z.
Article
CAS
PubMed
PubMed Central
Google Scholar
Skogberg G, Lundberg V, Berglund M, Gudmundsdottir J, Telemo E, Lindgren S, et al. Human thymic epithelial primary cells produce exosomes carrying tissue-restricted antigens. Immunol Cell Biol. 2015;93:727–34. https://doi.org/10.1038/icb.2015.33.
Article
CAS
PubMed
PubMed Central
Google Scholar
Lundberg V, Berglund M, Skogberg G, Lindgren S, Lundqvist C, Gudmundsdottir J, et al. Thymic exosomes promote the final maturation of thymocytes. Sci Rep. 2016;6:36479. https://doi.org/10.1038/srep36479.
Article
CAS
PubMed
PubMed Central
Google Scholar
Wang W, Wang L, Ruan L, Oh J, Dong X, Zhuge Q, et al. Extracellular vesicles extracted from young donor serum attenuate inflammaging via partially rejuvenating aged T-cell immunotolerance. Faseb J. 2018;32:fj201800059R. https://doi.org/10.1096/fj.201800059R.
Article
Google Scholar
Zhang X, Wang H, Claudio E, Brown K, Siebenlist U. A role for the IkappaB family member Bcl-3 in the control of central immunologic tolerance. Immunity. 2007;27:438–52. https://doi.org/10.1016/j.immuni.2007.07.017.
Article
CAS
PubMed
PubMed Central
Google Scholar
Hince M, Sakkal S, Vlahos K, Dudakov J, Boyd R, Chidgey A. The role of sex steroids and gonadectomy in the control of thymic involution. Cell Immunol. 2008;252:122–38. https://doi.org/10.1016/j.cellimm.2007.10.007.
Article
CAS
PubMed
Google Scholar
Velardi E, Dudakov JA, van den Brink MR. Sex steroid ablation: an immunoregenerative strategy for immunocompromised patients. Bone Marrow Transplant. 2015;50:S77–81. https://doi.org/10.1038/bmt.2015.101.
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
Du Q, Hoover A, Dozmorov I, Raj P, Khan S, Molina E, et al. MIR205HG is a long noncoding RNA that regulates growth hormone and prolactin production in the anterior pituitary. Dev Cell. 2019;49:618–31. https://doi.org/10.1016/j.devcel.2019.03.012.
Article
CAS
PubMed
Google Scholar
Paolino M, Koglgruber R, Cronin SJF, Uribesalgo I, Rauscher E, Harreiter J, et al. RANK links thymic regulatory T cells to fetal loss and gestational diabetes in pregnancy. Nature. 2020;589:442–7. https://doi.org/10.1038/s41586-020-03071-0.
Article
CAS
PubMed
PubMed Central
Google Scholar
Bredenkamp N, Nowell CS, Blackburn CC. Regeneration of the aged thymus by a single transcription factor. Development. 2014;141:1627–37. https://doi.org/10.1242/dev.103614.
Article
CAS
PubMed
PubMed Central
Google Scholar
Bredenkamp N, Ulyanchenko S, O’Neill KE, Manley NR, Vaidya HJ, Blackburn CC. An organized and functional thymus generated from FOXN1-reprogrammed fibroblasts. Nat Cell Biol. 2014;16:902–8. https://doi.org/10.1038/ncb3023.
Article
CAS
PubMed
PubMed Central
Google Scholar
Oh J, Wang W, Thomas R, Su D. Thymic rejuvenation via FOXN1-reprogrammed embryonic fibroblasts (FREFs) to counteract age-related inflammation. JCI insight. 2020;5: e140313. https://doi.org/10.1172/jci.insight.140313.
Article
PubMed Central
Google Scholar
Erickson M, Morkowski S, Lehar S, Gillard G, Beers C, Dooley J, et al. Regulation of thymic epithelium by keratinocyte growth factor. Blood. 2002;100:3269–78. https://doi.org/10.1182/blood-2002-04-1036.
Article
CAS
PubMed
Google Scholar
Min D, Panoskaltsis-Mortari A, Kuro OM, Hollander 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
Youm YH, Horvath TL, Mangelsdorf DJ, Kliewer SA, Dixit VD. Prolongevity hormone FGF21 protects against immune senescence by delaying age-related thymic involution. Proc Natl Acad Sci U S A. 2016;113:1026–31. https://doi.org/10.1073/pnas.1514511113.
Article
CAS
PubMed
PubMed Central
Google Scholar
Chaudhry MS, Velardi E, Dudakov JA, 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
Dudakov JA, Hanash AM, Jenq RR, Young LF, Ghosh A, Singer NV, et al. Interleukin-22 drives endogenous thymic regeneration in mice. Science. 2012;336:91–5. https://doi.org/10.1126/science.1218004.
Article
CAS
PubMed
PubMed Central
Google Scholar
Pan B, Wang D, Li L, Shang L, Xia F, Zhang F, et al. IL-22 accelerates thymus regeneration via stat3/mcl-1 and decreases chronic graft-versus-host disease in mice after allotransplants. Biol Blood Marrow Transplant. 2019;25:1911–9. https://doi.org/10.1016/j.bbmt.2019.06.002.
Article
CAS
PubMed
Google Scholar
Wertheimer T, Velardi E, Tsai J, Cooper K, Xiao S, Kloss CC, et al. Production of BMP4 by endothelial cells is crucial for endogenous thymic regeneration. Sci Immunol. 2018;3:eaal2736. https://doi.org/10.1126/sciimmunol.aal2736.
Article
PubMed
PubMed Central
Google Scholar
Chu YW, Schmitz S, Choudhury B, Telford W, Kapoor V, Garfield S, et al. Exogenous insulin-like growth factor 1 enhances thymopoiesis predominantly through thymic epithelial cell expansion. Blood. 2008;112:2836–46. https://doi.org/10.1182/blood-2008-04-149435.
Article
CAS
PubMed
PubMed Central
Google Scholar
Deng Y, Chen H, Zeng Y, Wang K, Zhang H, Hu H. Leaving no one behind: tracing every human thymocyte by single-cell RNA-sequencing. Semin Immunopathol. 2021;43:29–43. https://doi.org/10.1007/s00281-020-00834-9.
Article
CAS
PubMed
Google Scholar