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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2020
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.
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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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