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Liver X receptors are required for thymic resilience and T cell output
The thymus is a primary lymphoid organ necessary for optimal T cell development. Here, we show that liver X receptors (LXRs)—a class of nuclear receptors and transcription factors with diverse functions in metabolism and immunity—critically contribute to thymic integrity and function. LXRαβ-deficien...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537384/ https://www.ncbi.nlm.nih.gov/pubmed/32716519 http://dx.doi.org/10.1084/jem.20200318 |
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author | Chan, Christopher T. Fenn, Ashley M. Harder, Nina K. Mindur, John E. McAlpine, Cameron S. Patel, Jyoti Valet, Colin Rattik, Sara Iwamoto, Yoshiko He, Shun Anzai, Atsushi Kahles, Florian Poller, Wolfram C. Janssen, Henrike Wong, Lai Ping Fernandez-Hernando, Carlos Koolbergen, David R. van der Laan, Anja M. Yvan-Charvet, Laurent Sadreyev, Ruslan I. Nahrendorf, Matthias Westerterp, Marit Tall, Alan R. Gustafsson, Jan-Ake Swirski, Filip K. |
author_facet | Chan, Christopher T. Fenn, Ashley M. Harder, Nina K. Mindur, John E. McAlpine, Cameron S. Patel, Jyoti Valet, Colin Rattik, Sara Iwamoto, Yoshiko He, Shun Anzai, Atsushi Kahles, Florian Poller, Wolfram C. Janssen, Henrike Wong, Lai Ping Fernandez-Hernando, Carlos Koolbergen, David R. van der Laan, Anja M. Yvan-Charvet, Laurent Sadreyev, Ruslan I. Nahrendorf, Matthias Westerterp, Marit Tall, Alan R. Gustafsson, Jan-Ake Swirski, Filip K. |
author_sort | Chan, Christopher T. |
collection | PubMed |
description | The thymus is a primary lymphoid organ necessary for optimal T cell development. Here, we show that liver X receptors (LXRs)—a class of nuclear receptors and transcription factors with diverse functions in metabolism and immunity—critically contribute to thymic integrity and function. LXRαβ-deficient mice develop a fatty, rapidly involuting thymus and acquire a shrunken and prematurely immunoinhibitory peripheral T cell repertoire. LXRαβ’s functions are cell specific, and the resulting phenotypes are mutually independent. Although thymic macrophages require LXRαβ for cholesterol efflux, thymic epithelial cells (TECs) use LXRαβ for self-renewal and thymocytes for negative selection. Consequently, TEC-derived LXRαβ protects against homeostatic premature involution and orchestrates thymic regeneration following stress, while thymocyte-derived LXRαβ limits cell disposal during negative selection and confers heightened sensitivity to experimental autoimmune encephalomyelitis. These results identify three distinct but complementary mechanisms by which LXRαβ governs T lymphocyte education and illuminate LXRαβ’s indispensable roles in adaptive immunity. |
format | Online Article Text |
id | pubmed-7537384 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-75373842021-04-05 Liver X receptors are required for thymic resilience and T cell output Chan, Christopher T. Fenn, Ashley M. Harder, Nina K. Mindur, John E. McAlpine, Cameron S. Patel, Jyoti Valet, Colin Rattik, Sara Iwamoto, Yoshiko He, Shun Anzai, Atsushi Kahles, Florian Poller, Wolfram C. Janssen, Henrike Wong, Lai Ping Fernandez-Hernando, Carlos Koolbergen, David R. van der Laan, Anja M. Yvan-Charvet, Laurent Sadreyev, Ruslan I. Nahrendorf, Matthias Westerterp, Marit Tall, Alan R. Gustafsson, Jan-Ake Swirski, Filip K. J Exp Med Article The thymus is a primary lymphoid organ necessary for optimal T cell development. Here, we show that liver X receptors (LXRs)—a class of nuclear receptors and transcription factors with diverse functions in metabolism and immunity—critically contribute to thymic integrity and function. LXRαβ-deficient mice develop a fatty, rapidly involuting thymus and acquire a shrunken and prematurely immunoinhibitory peripheral T cell repertoire. LXRαβ’s functions are cell specific, and the resulting phenotypes are mutually independent. Although thymic macrophages require LXRαβ for cholesterol efflux, thymic epithelial cells (TECs) use LXRαβ for self-renewal and thymocytes for negative selection. Consequently, TEC-derived LXRαβ protects against homeostatic premature involution and orchestrates thymic regeneration following stress, while thymocyte-derived LXRαβ limits cell disposal during negative selection and confers heightened sensitivity to experimental autoimmune encephalomyelitis. These results identify three distinct but complementary mechanisms by which LXRαβ governs T lymphocyte education and illuminate LXRαβ’s indispensable roles in adaptive immunity. Rockefeller University Press 2020-07-27 /pmc/articles/PMC7537384/ /pubmed/32716519 http://dx.doi.org/10.1084/jem.20200318 Text en © 2020 Chan et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Chan, Christopher T. Fenn, Ashley M. Harder, Nina K. Mindur, John E. McAlpine, Cameron S. Patel, Jyoti Valet, Colin Rattik, Sara Iwamoto, Yoshiko He, Shun Anzai, Atsushi Kahles, Florian Poller, Wolfram C. Janssen, Henrike Wong, Lai Ping Fernandez-Hernando, Carlos Koolbergen, David R. van der Laan, Anja M. Yvan-Charvet, Laurent Sadreyev, Ruslan I. Nahrendorf, Matthias Westerterp, Marit Tall, Alan R. Gustafsson, Jan-Ake Swirski, Filip K. Liver X receptors are required for thymic resilience and T cell output |
title | Liver X receptors are required for thymic resilience and T cell output |
title_full | Liver X receptors are required for thymic resilience and T cell output |
title_fullStr | Liver X receptors are required for thymic resilience and T cell output |
title_full_unstemmed | Liver X receptors are required for thymic resilience and T cell output |
title_short | Liver X receptors are required for thymic resilience and T cell output |
title_sort | liver x receptors are required for thymic resilience and t cell output |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537384/ https://www.ncbi.nlm.nih.gov/pubmed/32716519 http://dx.doi.org/10.1084/jem.20200318 |
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