{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T11:47:57Z","timestamp":1790855277644,"version":"4.1.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2008,4,1]],"date-time":"2008-04-01T00:00:00Z","timestamp":1207008000000},"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":[[2008,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Medullary thymic epithelial cells (mTEC) play an important and unique role in central tolerance, expressing tissue-restricted Ags (TRA) which delete thymocytes autoreactive to peripheral organs. Since deficiencies in this cell type or activity can lead to devastating autoimmune diseases, it is important to understand the factors which regulate mTEC differentiation and function. Lymphotoxin (LT) ligands and the LT\u03b2R have been recently shown to be important regulators of mTEC biology; however, the precise role of this pathway in the thymus is not clear. In this study, we have investigated the impact of this signaling pathway in greater detail, focusing not only on mTEC but also on other thymic stromal cell subsets. LT\u03b2R expression was found in all TEC subsets, but the highest levels were detected in MTS-15+ thymic fibroblasts. Rather than directing the expression of the autoimmune regulator Aire in mTEC, we found LT\u03b2R signals were important for TRA expression in a distinct population of mTEC characterized by low levels of MHC class II (mTEClow), as well as maintenance of MTS-15+ fibroblasts. In addition, thymic stromal cell subsets from LT-deficient mice exhibit defects in chemokine production similar to that found in peripheral lymphoid organs of Lta\u2212\/\u2212 and Ltbr\u2212\/\u2212 mice. Thus, we propose a broader role for LT\u03b11\u03b22-LT\u03b2R signaling in the maintenance of the thymic microenvironments, specifically by regulating TRA and chemokine expression in mTEClow for efficient induction of central tolerance.<\/jats:p>","DOI":"10.4049\/jimmunol.180.8.5384","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T18:52:42Z","timestamp":1397847162000},"page":"5384-5392","source":"Crossref","is-referenced-by-count":97,"title":["The Lymphotoxin Pathway Regulates Aire-Independent Expression of Ectopic Genes and Chemokines in Thymic Stromal Cells"],"prefix":"10.1093","volume":"180","author":[{"given":"Natalie","family":"Seach","sequence":"first","affiliation":[{"name":"Monash Immunology and Stem Cell Laboratories, Monash University , Clayton ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoo","family":"Ueno","sequence":"additional","affiliation":[{"name":"Monash Immunology and Stem Cell Laboratories, Monash University , Clayton ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne L","family":"Fletcher","sequence":"additional","affiliation":[{"name":"Monash Immunology and Stem Cell Laboratories, Monash University , Clayton ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Lowen","sequence":"additional","affiliation":[{"name":"Monash Immunology and Stem Cell Laboratories, Monash University , Clayton ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Mattesich","sequence":"additional","affiliation":[{"name":"Bernard O\u2019Brien Institute of Microsurgery , Fitzroy ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian R","family":"Engwerda","sequence":"additional","affiliation":[{"name":"Queensland Institute of Medical Research , Herston, Queensland ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamish S","family":"Scott","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, Walter and Eliza Hall Institute of Medical Research , Parkville, Victoria ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl F","family":"Ware","sequence":"additional","affiliation":[{"name":"Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology , San Diego, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann P","family":"Chidgey","sequence":"additional","affiliation":[{"name":"Monash Immunology and Stem Cell Laboratories, Monash University , Clayton ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel H D","family":"Gray","sequence":"additional","affiliation":[{"name":"Joslin Diabetes Center , Boston, MA 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard L","family":"Boyd","sequence":"additional","affiliation":[{"name":"Monash Immunology and Stem Cell Laboratories, Monash University , Clayton ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,4,15]]},"reference":[{"key":"2026012809181067400_R1","first-page":"10","volume-title":"Immunol. 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