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The orphan nuclear receptor LRH-1/NR5a2 critically regulates T cell functions

LRH-1 (liver receptor homolog-1/NR5a2) is an orphan nuclear receptor, which regulates glucose and lipid metabolism, as well as intestinal inflammation via the transcriptional control of intestinal glucocorticoid synthesis. Predominantly expressed in epithelial cells, its expression and role in immun...

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Autores principales: Seitz, Carina, Huang, Juan, Geiselhöringer, Anna-Lena, Galbani-Bianchi, Pamela, Michalek, Svenja, Phan, Truong San, Reinhold, Cindy, Dietrich, Lea, Schmidt, Christian, Corazza, Nadia, Delgado, M. Eugenia, Schnalzger, Theresa, Schoonjans, Kristina, Brunner, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636985/
https://www.ncbi.nlm.nih.gov/pubmed/31328159
http://dx.doi.org/10.1126/sciadv.aav9732
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author Seitz, Carina
Huang, Juan
Geiselhöringer, Anna-Lena
Galbani-Bianchi, Pamela
Michalek, Svenja
Phan, Truong San
Reinhold, Cindy
Dietrich, Lea
Schmidt, Christian
Corazza, Nadia
Delgado, M. Eugenia
Schnalzger, Theresa
Schoonjans, Kristina
Brunner, Thomas
author_facet Seitz, Carina
Huang, Juan
Geiselhöringer, Anna-Lena
Galbani-Bianchi, Pamela
Michalek, Svenja
Phan, Truong San
Reinhold, Cindy
Dietrich, Lea
Schmidt, Christian
Corazza, Nadia
Delgado, M. Eugenia
Schnalzger, Theresa
Schoonjans, Kristina
Brunner, Thomas
author_sort Seitz, Carina
collection PubMed
description LRH-1 (liver receptor homolog-1/NR5a2) is an orphan nuclear receptor, which regulates glucose and lipid metabolism, as well as intestinal inflammation via the transcriptional control of intestinal glucocorticoid synthesis. Predominantly expressed in epithelial cells, its expression and role in immune cells are presently enigmatic. LRH-1 was found to be induced in immature and mature T lymphocytes upon stimulation. T cell–specific deletion of LRH-1 causes a drastic loss of mature peripheral T cells. LRH-1–depleted CD4(+) T cells exert strongly reduced activation-induced proliferation in vitro and in vivo and fail to mount immune responses against model antigens and to induce experimental intestinal inflammation. Similarly, LRH-1–deficient cytotoxic CD8(+) T cells fail to control viral infections. This study describes a novel and critical role of LRH-1 in T cell maturation, functions, and immopathologies and proposes LRH-1 as an emerging pharmacological target in the treatment of T cell–mediated inflammatory diseases.
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spelling pubmed-66369852019-07-19 The orphan nuclear receptor LRH-1/NR5a2 critically regulates T cell functions Seitz, Carina Huang, Juan Geiselhöringer, Anna-Lena Galbani-Bianchi, Pamela Michalek, Svenja Phan, Truong San Reinhold, Cindy Dietrich, Lea Schmidt, Christian Corazza, Nadia Delgado, M. Eugenia Schnalzger, Theresa Schoonjans, Kristina Brunner, Thomas Sci Adv Research Articles LRH-1 (liver receptor homolog-1/NR5a2) is an orphan nuclear receptor, which regulates glucose and lipid metabolism, as well as intestinal inflammation via the transcriptional control of intestinal glucocorticoid synthesis. Predominantly expressed in epithelial cells, its expression and role in immune cells are presently enigmatic. LRH-1 was found to be induced in immature and mature T lymphocytes upon stimulation. T cell–specific deletion of LRH-1 causes a drastic loss of mature peripheral T cells. LRH-1–depleted CD4(+) T cells exert strongly reduced activation-induced proliferation in vitro and in vivo and fail to mount immune responses against model antigens and to induce experimental intestinal inflammation. Similarly, LRH-1–deficient cytotoxic CD8(+) T cells fail to control viral infections. This study describes a novel and critical role of LRH-1 in T cell maturation, functions, and immopathologies and proposes LRH-1 as an emerging pharmacological target in the treatment of T cell–mediated inflammatory diseases. American Association for the Advancement of Science 2019-07-17 /pmc/articles/PMC6636985/ /pubmed/31328159 http://dx.doi.org/10.1126/sciadv.aav9732 Text en Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Research Articles
Seitz, Carina
Huang, Juan
Geiselhöringer, Anna-Lena
Galbani-Bianchi, Pamela
Michalek, Svenja
Phan, Truong San
Reinhold, Cindy
Dietrich, Lea
Schmidt, Christian
Corazza, Nadia
Delgado, M. Eugenia
Schnalzger, Theresa
Schoonjans, Kristina
Brunner, Thomas
The orphan nuclear receptor LRH-1/NR5a2 critically regulates T cell functions
title The orphan nuclear receptor LRH-1/NR5a2 critically regulates T cell functions
title_full The orphan nuclear receptor LRH-1/NR5a2 critically regulates T cell functions
title_fullStr The orphan nuclear receptor LRH-1/NR5a2 critically regulates T cell functions
title_full_unstemmed The orphan nuclear receptor LRH-1/NR5a2 critically regulates T cell functions
title_short The orphan nuclear receptor LRH-1/NR5a2 critically regulates T cell functions
title_sort orphan nuclear receptor lrh-1/nr5a2 critically regulates t cell functions
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636985/
https://www.ncbi.nlm.nih.gov/pubmed/31328159
http://dx.doi.org/10.1126/sciadv.aav9732
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