{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:27:07Z","timestamp":1790393227868,"version":"4.1.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2011,8,1]],"date-time":"2011-08-01T00:00:00Z","timestamp":1312156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Autoimmune polyendocrinopathy\u2013candidiasis\u2013ectodermal dystrophy (APECED) is a monogenic autoimmune disease that is caused by mutations in the AIRE gene. Murine studies have linked AIRE to thymocyte selection and peripheral deletional tolerance, but the pathogenesis of the human disease remains unclear. In this study, we show that APECED patients have elevated IL-7 levels and a drastically decreased expression of IL-7R on CD8+ T cells. This is associated with increased proliferation and a decreased expression of the negative TCR regulator CD5 in the CD45RO\u2212 subset. The CD45RO\u2212 cells also display oligoclonal expansions, decreased expression of the lymph node homing factors CCR7 and CD62L, and increased expression of perforin, consistent with the accumulation of highly differentiated effector cells. The CD45RO\u2212CCR7+CD8+ population of cells with markers characteristic of naive phenotype is also skewed, as shown by decreased expression of CD5 and increased expression of perforin. The putative CD31+ recent thymic emigrant population is likewise affected. These data are consistent with IL-7 dysregulation inducing a decreased threshold of TCR signaling and self-antigen\u2013driven proliferation, probably in synergy with the failed thymic selection. The resultant loss of CD8+ T cell homeostasis is likely to play a significant role in the pathogenesis of APECED. Our findings may also hold lessons for other diseases in which the IL-7\u2013IL-7R pathway has emerged as a risk factor.<\/jats:p>","DOI":"10.4049\/jimmunol.1100212","type":"journal-article","created":{"date-parts":[[2011,7,14]],"date-time":"2011-07-14T03:59:38Z","timestamp":1310615978000},"page":"2023-2030","source":"Crossref","is-referenced-by-count":38,"title":["IL-7 Dysregulation and Loss of CD8+ T Cell Homeostasis in the Monogenic Human Disease Autoimmune Polyendocrinopathy\u2013Candidiasis\u2013Ectodermal Dystrophy"],"prefix":"10.1093","volume":"187","author":[{"given":"Sini M","family":"Laakso","sequence":"first","affiliation":[{"name":"Department of Immunology, Haartman Institute, University of Helsinki , 00014 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliisa","family":"Kek\u00e4l\u00e4inen","sequence":"additional","affiliation":[{"name":"Department of Immunology, Haartman Institute, University of Helsinki , 00014 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura H","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Immunology, Haartman Institute, University of Helsinki , 00014 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuisku-Tuulia","family":"Laurinolli","sequence":"additional","affiliation":[{"name":"Department of Immunology, Haartman Institute, University of Helsinki , 00014 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helga","family":"Mannerstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Immunology, Haartman Institute, University of Helsinki , 00014 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelli","family":"Heikkil\u00e4","sequence":"additional","affiliation":[{"name":"Department of Immunology, Haartman Institute, University of Helsinki , 00014 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anni","family":"Lehtoviita","sequence":"additional","affiliation":[{"name":"Department of Immunology, Haartman Institute, University of Helsinki , 00014 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaakko","family":"Perheentupa","sequence":"additional","affiliation":[{"name":"Hospital for Children and Adolescents, Helsinki University Hospital , 00029 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Jarva","sequence":"additional","affiliation":[{"name":"Department of Immunology, Haartman Institute, University of Helsinki , 00014 Helsinki ,","place":["Finland"]},{"name":"Helsinki University Hospital Laboratory, Helsinki University Hospital , 00029 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T Petteri","family":"Arstila","sequence":"additional","affiliation":[{"name":"Department of Immunology, Haartman Institute, University of Helsinki , 00014 Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,8,15]]},"reference":[{"key":"2025032410264577000_r1","doi-asserted-by":"crossref","first-page":"2843","DOI":"10.1210\/jc.2005-2611","article-title":"Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy","volume":"91","author":"Perheentupa","year":"2006","journal-title":"J. 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