Takahama Y. Journey through the thymus: stromal guides for T-cell development and selection. Nat Rev Immunol. 2006;6:127–35.

Article  PubMed  CAS  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.

Article  PubMed  CAS  Google Scholar 

Kyewski B, Derbinski J. Self-representation in the thymus: an extended view. Nat Rev Immunol. 2004;4:688–98.

Article  PubMed  CAS  Google Scholar 

Ramsey C, Winqvist O, Puhakka L, Halonen M, Moro A, Kampe O, et al. Aire deficient mice develop multiple features of APECED phenotype and show altered immune response. Hum Mol Genet. 2002;11:397–409.

Article  PubMed  CAS  Google Scholar 

Anderson MS, Venanzi ES, Klein L, Chen Z, Berzins SP, Turley SJ, et al. Projection of an immunological self shadow within the thymus by the aire protein. Science. 2002;298:1395–401.

Article  PubMed  CAS  Google Scholar 

Wells KL, Miller CN, Gschwind AR, Wei W, Phipps JD, Anderson MS, et al. Combined transient ablation and single-cell RNA-sequencing reveals the development of medullary thymic epithelial cells. Elife. 2020;9:e60188.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Michelson DA, Hase K, Kaisho T, Benoist C, Mathis D. Thymic epithelial cells co-opt lineage-defining transcription factors to eliminate autoreactive T cells. Cell. 2022;185:2542–58 e18.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Dhalla F, Baran-Gale J, Maio S, Chappell L, Hollander GA, Ponting CP. Biologically indeterminate yet ordered promiscuous gene expression in single medullary thymic epithelial cells. EMBO J. 2020;39:e101828.

Article  PubMed  CAS  Google Scholar 

Miller CN, Proekt I, von Moltke J, Wells KL, Rajpurkar AR, Wang H, et al. Thymic tuft cells promote an IL-4- enriched medulla and shape thymocyte development. Nature. 2018;559:627–31.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Bornstein C, Nevo S, Giladi A, Kadouri N, Pouzolles M, Gerbe F, et al. Single-cell mapping of the thymic stroma identifies IL-25-producing tuft epithelial cells. Nature. 2018;559:622–6.

Article  PubMed  CAS  Google Scholar 

Michelson DA, Mathis D. Thymic mimetic cells: tolerogenic masqueraders. Trends Immunol. 2022;43:782–91.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Chuprin A, Avin A, Goldfarb Y, Herzig Y, Levi B, Jacob A, et al. The deacetylase Sirt1 is an essential regulator of Aire-mediated induction of central immunological tolerance. Nat Immunol. 2015;16:737–45.

Article  PubMed  CAS  Google Scholar 

Matsumoto M, Nishikawa Y, Nishijima H, Morimoto J, Matsumoto M, Mouri Y. Which model better fits the role of aire in the establishment of self-tolerance: the transcription model or the maturation model? Front Immunol. 2013;4:210.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Giraud M, Yoshida H, Abramson J, Rahl PB, Young RA, Mathis D, et al. Aire unleashes stalled RNA polymerase to induce ectopic gene expression in thymic epithelial cells. Proc Natl Acad Sci USA. 2012;109:535–40.

Article  PubMed  CAS  Google Scholar 

Danso-Abeam D, Humblet-Baron S, Dooley J, Liston A. Models of aire-dependent gene regulation for thymic negative selection. Front Immunol. 2011;2:14.

Article  PubMed  PubMed Central  Google Scholar 

Abramson J, Giraud M, Benoist C, Mathis D. Aire’s partners in the molecular control of immunological tolerance. Cell. 2010;140:123–35.

Article  PubMed  CAS  Google Scholar 

Anderson AO, Shaw S. Conduit for privileged communications in the lymph node. Immunity. 2005;22:3–5.

Article  PubMed  CAS  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.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Bansal K, Yoshida H, Benoist C, Mathis D. The transcriptional regulator Aire binds to and activates superenhancers. Nat Immunol. 2017;18:263–73.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Guerau-de-Arellano M, Martinic M, Benoist C, Mathis D. Neonatal tolerance revisited: a perinatal window for Aire control of autoimmunity. J Exp Med. 2009;206:1245–52.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Gabler J, Arnold J, Kyewski B. Promiscuous gene expression and the developmental dynamics of medullary thymic epithelial cells. Eur J Immunol. 2007;37:3363–72.

Article  PubMed  Google Scholar 

Yang S, Fujikado N, Kolodin D, Benoist C, Mathis D. Immune tolerance. Regulatory T cells generated early in life play a distinct role in maintaining self-tolerance. Science. 2015;348:589–94.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Baran-Gale J, Morgan MD, Maio S, Dhalla F, Calvo-Asensio I, Deadman ME, et al. Ageing compromises mouse thymus function and remodels epithelial cell differentiation. Elife. 2020;9:e56221.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Herzig Y, Nevo S, Bornstein C, Brezis MR, Ben-Hur S, Shkedy A, et al. Transcriptional programs that control expression of the autoimmune regulator gene Aire. Nat Immunol. 2017;18:161–72.

Article  PubMed  CAS  Google Scholar 

Gierl MS, Karoulias N, Wende H, Strehle M, Birchmeier C. The zinc-finger factor Insm1 (IA-1) is essential for the development of pancreatic beta cells and intestinal endocrine cells. Genes Dev. 2006;20:2465–78.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Jia S, Wildner H, Birchmeier C. Insm1 controls the differentiation of pulmonary neuroendocrine cells by repressing Hes1. Dev Biol. 2015;408:90–8.

Article  PubMed  CAS  Google Scholar 

Jia S, Ivanov A, Blasevic D, Muller T, Purfurst B, Sun W, et al. Insm1 cooperates with Neurod1 and Foxa2 to maintain mature pancreatic beta-cell function. EMBO J. 2015;34:1417–33.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Welcker JE, Hernandez-Miranda LR, Paul FE, Jia S, Ivanov A, Selbach M, et al. Insm1 controls development of pituitary endocrine cells and requires a SNAG domain for function and for recruitment of histone-modifying factors. Development. 2013;140:4947–58.

Article  PubMed  CAS  Google Scholar 

Anderson G, Baik S, Cowan JE, Holland AM, McCarthy NI, Nakamura K, et al. Mechanisms of thymus medulla development and function. Curr Top Microbiol Immunol. 2014;373:19–47.

PubMed  CAS  Google Scholar 

Derbinski J, Schulte A, Kyewski B, Klein L. Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self. Nat Immunol. 2001;2:1032–9.

Article  PubMed  CAS  Google Scholar 

Tomofuji Y, Takaba H, Suzuki HI, Benlaribi R, Martinez CDP, Abe Y, et al. Chd4 choreographs self-antigen expression for central immune tolerance. Nat Immunol. 2020;21:892–901.

Article  PubMed  CAS  Google Scholar 

Takaba H, Morishita Y, Tomofuji Y, Danks L, Nitta T, Komatsu N, et al. Fezf2 Orchestrates a Thymic Program of Self-Antigen Expression for Immune Tolerance. Cell. 2015;163:975–87.

Article  PubMed  CAS  Google Scholar 

Lattin JE, Schroder K, Su AI, Walker JR, Zhang J, Wiltshire T, et al. Expression analysis of G Protein-Coupled Receptors in mouse macrophages. Immunome Res. 2008;4:5.

Article  PubMed  PubMed Central  Google Scholar 

Goldfarb Y, Givony T, Kadouri N, Dobes J, Peligero-Cruz C, Zalayat I, et al. Mechanistic dissection of dominant AIRE mutations in mouse models reveals AIRE autoregulation. J Exp Med. 2021;218:e20201076.

Article  PubMed  PubMed Central  CAS  Google Scholar 

LaFlam TN, Seumois G, Miller CN, Lwin W, Fasano KJ, Waterfield M, et al. Identification of a novel cisregulatory element essential for immune tolerance. J Exp Med. 2015;212:1993–2002.

Article  PubMed  PubMed Central  CAS