{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:23:20Z","timestamp":1792002200242,"version":"4.4.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"vor","delay-in-days":4041,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>In the thymus, interactions with both cortical and medullary microenvironments regulate the development of self-tolerant conventional CD4+ and CD8+ \u03b1\u03b2T cells expressing a wide range of \u03b1\u03b2TCR specificities. Additionally, the cortex is also required for the development of invariant NKT (iNKT) cells, a specialized subset of T cells that expresses a restricted \u03b1\u03b2TCR repertoire and is linked to the regulation of innate and adaptive immune responses. Although the role of the cortex in this process is to enable recognition of CD1d molecules expressed by CD4+CD8+ thymocyte precursors, the requirements for additional thymus microenvironments during iNKT cell development are unknown. In this study, we reveal a role for medullary thymic epithelial cells (mTECs) during iNKT cell development in the mouse thymus. This requirement for mTECs correlates with their expression of genes required for IL-15 trans-presentation, and we show that soluble IL-15\/IL-15R\u03b1 complexes restore iNKT cell development in the absence of mTECs. Furthermore, mTEC development is abnormal in iNKT cell\u2013deficient mice, and early stages in iNKT cell development trigger receptor activator for NF-\u03baB ligand\u2013mediated mTEC development. Collectively, our findings demonstrate that intrathymic iNKT cell development requires stepwise interactions with both the cortex and the medulla, emphasizing the importance of thymus compartmentalization in the generation of both diverse and invariant \u03b1\u03b2T cells. Moreover, the identification of a novel requirement for iNKT cells in thymus medulla development further highlights the role of both innate and adaptive immune cells in thymus medulla formation.<\/jats:p>","DOI":"10.4049\/jimmunol.1303057","type":"journal-article","created":{"date-parts":[[2014,2,8]],"date-time":"2014-02-08T07:33:41Z","timestamp":1391844821000},"page":"2659-2666","source":"Crossref","is-referenced-by-count":106,"title":["An Essential Role for Medullary Thymic Epithelial Cells during the Intrathymic Development of Invariant NKT Cells"],"prefix":"10.1093","volume":"192","author":[{"given":"Andrea J","family":"White","sequence":"first","affiliation":[{"name":"Medical Research Council Centre for Immune Regulation, Institute for Biomedical Research, University of Birmingham , Birmingham B15 2TT,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William E","family":"Jenkinson","sequence":"additional","affiliation":[{"name":"Medical Research Council Centre for Immune Regulation, Institute for Biomedical Research, University of Birmingham , Birmingham B15 2TT,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer E","family":"Cowan","sequence":"additional","affiliation":[{"name":"Medical Research Council Centre for Immune Regulation, Institute for Biomedical Research, University of Birmingham , Birmingham B15 2TT,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia M","family":"Parnell","sequence":"additional","affiliation":[{"name":"Medical Research Council Centre for Immune Regulation, Institute for Biomedical Research, University of Birmingham , Birmingham B15 2TT,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Bacon","sequence":"additional","affiliation":[{"name":"Medical Research Council Centre for Immune Regulation, Institute for Biomedical Research, University of Birmingham , Birmingham B15 2TT,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick D","family":"Jones","sequence":"additional","affiliation":[{"name":"Medical Research Council Centre for Immune Regulation, Institute for Biomedical Research, University of Birmingham , Birmingham B15 2TT,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric J","family":"Jenkinson","sequence":"additional","affiliation":[{"name":"Medical Research Council Centre for Immune Regulation, Institute for Biomedical Research, University of Birmingham , Birmingham B15 2TT,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham","family":"Anderson","sequence":"additional","affiliation":[{"name":"Medical Research Council Centre for Immune Regulation, Institute for Biomedical Research, University of Birmingham , Birmingham B15 2TT,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,3,15]]},"reference":[{"key":"2025032404194992600_r1","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1111\/j.0105-2896.2006.00348.x","article-title":"Central tolerance: good but imperfect","volume":"209","author":"Gallegos","year":"2006","journal-title":"Immunol. 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