{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T17:08:51Z","timestamp":1779469731934,"version":"3.53.1"},"reference-count":77,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"National Institutes of Health\/National Institute of Allergy and Infectious Diseases","award":["R01\/R56 AI123396"],"award-info":[{"award-number":["R01\/R56 AI123396"]}]},{"name":"University of Chicago Initiative for Maximizing Student Development","award":["R25 GM109439"],"award-info":[{"award-number":["R25 GM109439"]}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32 AI007090"],"award-info":[{"award-number":["T32 AI007090"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical Scientist National Research Service","award":["T32 GM150375"],"award-info":[{"award-number":["T32 GM150375"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Invariant natural killer T 1 (iNKT1) cells are prototypic interferon \u03b3\u2013producing, innate-like T lymphocytes that play crucial roles in protection against pathogen infection and cancer. In the thymus, where these cells develop, iNKT cells contribute to the recruitment of antigen-presenting cells and promote T cell tolerance. Although the transcriptional programs guiding iNKT cell specification are well characterized, the mechanisms directing their subsequent maturation and tissue-associated effector functions remain poorly understood. Here, we reveal that the transcription factor Ets1 is essential for the maintenance of thymic iNKT1 cells and for their differentiation into a CD103+ transforming growth factor \u03b21\u2013dependent, tissue-resident phenotype, in addition to playing a critical role in maintaining iNKT1 effector function in the liver and spleen. Mechanistically, Ets1 limits the expression of CD8 effector T cell\u2013associated genes and restricts the induction of the transcription factor Tbet. Elevated Tbet expression partially rescues thymic iNKT1 cell numbers in the absence of Ets1 but shifts their differentiation toward a migratory, CD103\u2212 pathway. In peripheral tissues, elevated Tbet expression failed to overcome the requirement for Ets1 in activation-induced interferon \u03b3\u2013production but instead drove increased cytotoxic effector protein expression. Our findings establish Ets1 as a central regulator of iNKT1 cell homeostasis, enforcing a tissue-resident identity in the thymus and supporting context-appropriate effector function.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag024","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T09:54:37Z","timestamp":1773827677000},"source":"Crossref","is-referenced-by-count":0,"title":["Development and function of specified thymic iNKT1 cells critically depend on an Ets1-Tbet transcription factor axis"],"prefix":"10.1093","volume":"215","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9006-9225","authenticated-orcid":false,"given":"Roy C","family":"Morgan","sequence":"first","affiliation":[{"name":"Committee on Genetics, Genomics, and Systems Biology, University of Chicago , Chicago, IL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron","family":"Frank","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Chicago , Chicago, IL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Li","sequence":"additional","affiliation":[{"name":"Committee on Immunology, University of Chicago , Chicago, IL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezra","family":"Moos","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Chicago , Chicago, IL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1124-2024","authenticated-orcid":false,"given":"Mary","family":"Attaway","sequence":"additional","affiliation":[{"name":"Committee on Immunology, University of Chicago , Chicago, IL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randy A","family":"Melanson","sequence":"additional","affiliation":[{"name":"Committee on Immunology, University 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Genetics, Genomics, and Systems Biology, University of Chicago , Chicago, IL,","place":["United States"]},{"name":"Department of Pathology, University of Chicago , Chicago, IL,","place":["United States"]},{"name":"Committee on Immunology, University of Chicago , Chicago, IL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8527-7276","authenticated-orcid":false,"given":"Mikael","family":"Sigvardsson","sequence":"additional","affiliation":[{"name":"Department of Molecular Hematology, University of Lund , Lund,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth T","family":"Bartom","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University , Chicago, IL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara 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