{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:42:33Z","timestamp":1792183353702,"version":"4.4.0"},"reference-count":79,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T00:00:00Z","timestamp":1645401600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T00:00:00Z","timestamp":1645401600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T00:00:00Z","timestamp":1645401600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010665","name":"H2020 Marie Sk\u0142odowska-Curie Actions","doi-asserted-by":"publisher","award":["CIG_SIGnEPI4Tol_618541"],"award-info":[{"award-number":["CIG_SIGnEPI4Tol_618541"]}],"id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["2011-CHEX-001-R12004KK"],"award-info":[{"award-number":["2011-CHEX-001-R12004KK"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-19-CE18-0021-01 RANKLthym"],"award-info":[{"award-number":["ANR-19-CE18-0021-01 RANKLthym"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2022,1,14]]},"abstract":"<jats:p>\n                    Interactions of developing T cells with Aire\n                    <jats:sup>+<\/jats:sup>\n                    medullary thymic epithelial cells expressing high levels of MHCII molecules (mTEC\n                    <jats:sup>hi<\/jats:sup>\n                    ) are critical for the induction of central tolerance in the thymus. In turn, thymocytes regulate the cellularity of Aire\n                    <jats:sup>+<\/jats:sup>\n                    mTEC\n                    <jats:sup>hi<\/jats:sup>\n                    . However, it remains unknown whether thymocytes control the precursors of Aire\n                    <jats:sup>+<\/jats:sup>\n                    mTEC\n                    <jats:sup>hi<\/jats:sup>\n                    that are contained in mTEC\n                    <jats:sup>lo<\/jats:sup>\n                    cells or other mTEC\n                    <jats:sup>lo<\/jats:sup>\n                    subsets that have recently been delineated by single-cell transcriptomic analyses. Here, using three distinct transgenic mouse models, in which antigen presentation between mTECs and CD4\n                    <jats:sup>+<\/jats:sup>\n                    thymocytes is perturbed, we show by high-throughput RNA-seq that self-reactive CD4\n                    <jats:sup>+<\/jats:sup>\n                    thymocytes induce key transcriptional regulators in mTEC\n                    <jats:sup>lo<\/jats:sup>\n                    and control the composition of mTEC\n                    <jats:sup>lo<\/jats:sup>\n                    subsets, including Aire\n                    <jats:sup>+<\/jats:sup>\n                    mTEC\n                    <jats:sup>hi<\/jats:sup>\n                    precursors, post-Aire and tuft-like mTECs. Furthermore, these interactions upregulate the expression of tissue-restricted self-antigens, cytokines, chemokines, and adhesion molecules important for T-cell development. This gene activation program induced in mTEC\n                    <jats:sup>lo<\/jats:sup>\n                    is combined with a global increase of the active H3K4me3 histone mark. Finally, we demonstrate that these self-reactive interactions between CD4\n                    <jats:sup>+<\/jats:sup>\n                    thymocytes and mTECs critically prevent multiorgan autoimmunity. Our genome-wide study thus reveals that self-reactive CD4\n                    <jats:sup>+<\/jats:sup>\n                    thymocytes control multiple unsuspected facets from immature stages of mTECs, which determines their heterogeneity.\n                  <\/jats:p>","DOI":"10.7554\/elife.69982","type":"journal-article","created":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T06:15:13Z","timestamp":1642140913000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.69982","source":"Crossref","is-referenced-by-count":25,"title":["Thymocytes trigger self-antigen-controlling pathways in immature medullary thymic epithelial stages"],"prefix":"10.7554","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6296-8426","authenticated-orcid":true,"given":"Noella","family":"Lopes","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/035xkbk20","id-type":"ROR","asserted-by":"publisher"}],"name":"Aix-Marseille University, CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy","place":["Marseille, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Boucherit","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/035xkbk20","id-type":"ROR","asserted-by":"publisher"}],"name":"Aix-Marseille University, CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy","place":["Marseille, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7613-3668","authenticated-orcid":true,"given":"J\u00e9r\u00e9my C","family":"Santamaria","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/035xkbk20","id-type":"ROR","asserted-by":"publisher"}],"name":"Aix-Marseille University, CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy","place":["Marseille, 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de Marseille-Luminy","place":["Marseille, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1208-9677","authenticated-orcid":true,"given":"Matthieu","family":"Giraud","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03gnr7b55","id-type":"ROR","asserted-by":"publisher"}],"name":"Nantes Universit\u00e9, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064","place":["Nantes, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8803-9708","authenticated-orcid":true,"given":"Magali","family":"Irla","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/035xkbk20","id-type":"ROR","asserted-by":"publisher"}],"name":"Aix-Marseille University, CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy","place":["Marseille, 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