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RORγt and RORα signature genes in human Th17 cells
RORγt and RORα are transcription factors of the RAR-related orphan nuclear receptor (ROR) family. They are expressed in Th17 cells and have been suggested to play a role in Th17 differentiation. Although RORγt signature genes have been characterized in mouse Th17 cells, detailed information on its t...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538713/ https://www.ncbi.nlm.nih.gov/pubmed/28763457 http://dx.doi.org/10.1371/journal.pone.0181868 |
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author | Castro, Glenda Liu, Xuejun Ngo, Karen De Leon-Tabaldo, Aimee Zhao, Shanrong Luna-Roman, Rosa Yu, Jingxue Cao, Tinghua Kuhn, Robert Wilkinson, Patrick Herman, Krystal Nelen, Marina I. Blevitt, Jonathan Xue, Xiaohua Fourie, Anne Fung-Leung, Wai-Ping |
author_facet | Castro, Glenda Liu, Xuejun Ngo, Karen De Leon-Tabaldo, Aimee Zhao, Shanrong Luna-Roman, Rosa Yu, Jingxue Cao, Tinghua Kuhn, Robert Wilkinson, Patrick Herman, Krystal Nelen, Marina I. Blevitt, Jonathan Xue, Xiaohua Fourie, Anne Fung-Leung, Wai-Ping |
author_sort | Castro, Glenda |
collection | PubMed |
description | RORγt and RORα are transcription factors of the RAR-related orphan nuclear receptor (ROR) family. They are expressed in Th17 cells and have been suggested to play a role in Th17 differentiation. Although RORγt signature genes have been characterized in mouse Th17 cells, detailed information on its transcriptional control in human Th17 cells is limited and even less is known about RORα signature genes which have not been reported in either human or mouse T cells. In this study, global gene expression of human CD4 T cells activated under Th17 skewing conditions was profiled by RNA sequencing. RORγt and RORα signature genes were identified in these Th17 cells treated with specific siRNAs to knock down RORγt or RORα expression. We have generated selective small molecule RORγt modulators and they were also utilized as pharmacological tools in RORγt signature gene identification. Our results showed that RORγt controlled the expression of a very selective number of genes in Th17 cells and most of them were regulated by RORα as well albeit a weaker influence. Key Th17 genes including IL-17A, IL-17F, IL-23R, CCL20 and CCR6 were shown to be regulated by both RORγt and RORα. Our results demonstrated an overlapping role of RORγt and RORα in human Th17 cell differentiation through regulation of a defined common set of Th17 genes. RORγt as a drug target for treatment of Th17 mediated autoimmune diseases such as psoriasis has been demonstrated recently in clinical trials. Our results suggest that RORα could be involved in same disease mechanisms and gene signatures identified in this report could be valuable biomarkers for tracking the pharmacodynamic effects of compounds that modulate RORγt or RORα activities in patients. |
format | Online Article Text |
id | pubmed-5538713 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-55387132017-08-07 RORγt and RORα signature genes in human Th17 cells Castro, Glenda Liu, Xuejun Ngo, Karen De Leon-Tabaldo, Aimee Zhao, Shanrong Luna-Roman, Rosa Yu, Jingxue Cao, Tinghua Kuhn, Robert Wilkinson, Patrick Herman, Krystal Nelen, Marina I. Blevitt, Jonathan Xue, Xiaohua Fourie, Anne Fung-Leung, Wai-Ping PLoS One Research Article RORγt and RORα are transcription factors of the RAR-related orphan nuclear receptor (ROR) family. They are expressed in Th17 cells and have been suggested to play a role in Th17 differentiation. Although RORγt signature genes have been characterized in mouse Th17 cells, detailed information on its transcriptional control in human Th17 cells is limited and even less is known about RORα signature genes which have not been reported in either human or mouse T cells. In this study, global gene expression of human CD4 T cells activated under Th17 skewing conditions was profiled by RNA sequencing. RORγt and RORα signature genes were identified in these Th17 cells treated with specific siRNAs to knock down RORγt or RORα expression. We have generated selective small molecule RORγt modulators and they were also utilized as pharmacological tools in RORγt signature gene identification. Our results showed that RORγt controlled the expression of a very selective number of genes in Th17 cells and most of them were regulated by RORα as well albeit a weaker influence. Key Th17 genes including IL-17A, IL-17F, IL-23R, CCL20 and CCR6 were shown to be regulated by both RORγt and RORα. Our results demonstrated an overlapping role of RORγt and RORα in human Th17 cell differentiation through regulation of a defined common set of Th17 genes. RORγt as a drug target for treatment of Th17 mediated autoimmune diseases such as psoriasis has been demonstrated recently in clinical trials. Our results suggest that RORα could be involved in same disease mechanisms and gene signatures identified in this report could be valuable biomarkers for tracking the pharmacodynamic effects of compounds that modulate RORγt or RORα activities in patients. Public Library of Science 2017-08-01 /pmc/articles/PMC5538713/ /pubmed/28763457 http://dx.doi.org/10.1371/journal.pone.0181868 Text en © 2017 Castro et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Castro, Glenda Liu, Xuejun Ngo, Karen De Leon-Tabaldo, Aimee Zhao, Shanrong Luna-Roman, Rosa Yu, Jingxue Cao, Tinghua Kuhn, Robert Wilkinson, Patrick Herman, Krystal Nelen, Marina I. Blevitt, Jonathan Xue, Xiaohua Fourie, Anne Fung-Leung, Wai-Ping RORγt and RORα signature genes in human Th17 cells |
title | RORγt and RORα signature genes in human Th17 cells |
title_full | RORγt and RORα signature genes in human Th17 cells |
title_fullStr | RORγt and RORα signature genes in human Th17 cells |
title_full_unstemmed | RORγt and RORα signature genes in human Th17 cells |
title_short | RORγt and RORα signature genes in human Th17 cells |
title_sort | rorγt and rorα signature genes in human th17 cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538713/ https://www.ncbi.nlm.nih.gov/pubmed/28763457 http://dx.doi.org/10.1371/journal.pone.0181868 |
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