CD4+ T cells from children with active juvenile idiopathic arthritis show altered chromatin features associated with transcriptional abnormalities

Abstract Juvenile idiopathic arthritis (JIA) is one of the most common chronic diseases in children. While clinical outcomes for patients with juvenile JIA have improved, the underlying biology of the disease and mechanisms underlying therapeutic response/non-response are poorly understood. We have...

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Autores principales:	Evan Tarbell, Kaiyu Jiang, Teresa R. Hennon, Lucy Holmes, Sonja Williams, Yao Fu, Patrick M. Gaffney, Tao Liu, James N. Jarvis
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0e8fdf375c2a4a7794e76c20764ae53c
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spelling	oai:doaj.org-article:0e8fdf375c2a4a7794e76c20764ae53c2021-12-02T14:03:57ZCD4+ T cells from children with active juvenile idiopathic arthritis show altered chromatin features associated with transcriptional abnormalities10.1038/s41598-021-82989-52045-2322https://doaj.org/article/0e8fdf375c2a4a7794e76c20764ae53c2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82989-5https://doaj.org/toc/2045-2322Abstract Juvenile idiopathic arthritis (JIA) is one of the most common chronic diseases in children. While clinical outcomes for patients with juvenile JIA have improved, the underlying biology of the disease and mechanisms underlying therapeutic response/non-response are poorly understood. We have shown that active JIA is associated with distinct transcriptional abnormalities, and that the attainment of remission is associated with reorganization of transcriptional networks. In this study, we used a multi-omics approach to identify mechanisms driving the transcriptional abnormalities in peripheral blood CD4+ T cells of children with active JIA. We demonstrate that active JIA is associated with alterations in CD4+ T cell chromatin, as assessed by ATACseq studies. However, 3D chromatin architecture, assessed by HiChIP and simultaneous mapping of CTCF anchors of chromatin loops, reveals that normal 3D chromatin architecture is largely preserved. Overlapping CTCF binding, ATACseq, and RNAseq data with known JIA genetic risk loci demonstrated the presence of genetic influences on the observed transcriptional abnormalities and identified candidate target genes. These studies demonstrate the utility of multi-omics approaches for unraveling important questions regarding the pathobiology of autoimmune diseases.Evan TarbellKaiyu JiangTeresa R. HennonLucy HolmesSonja WilliamsYao FuPatrick M. GaffneyTao LiuJames N. JarvisNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Evan Tarbell Kaiyu Jiang Teresa R. Hennon Lucy Holmes Sonja Williams Yao Fu Patrick M. Gaffney Tao Liu James N. Jarvis CD4+ T cells from children with active juvenile idiopathic arthritis show altered chromatin features associated with transcriptional abnormalities
description	Abstract Juvenile idiopathic arthritis (JIA) is one of the most common chronic diseases in children. While clinical outcomes for patients with juvenile JIA have improved, the underlying biology of the disease and mechanisms underlying therapeutic response/non-response are poorly understood. We have shown that active JIA is associated with distinct transcriptional abnormalities, and that the attainment of remission is associated with reorganization of transcriptional networks. In this study, we used a multi-omics approach to identify mechanisms driving the transcriptional abnormalities in peripheral blood CD4+ T cells of children with active JIA. We demonstrate that active JIA is associated with alterations in CD4+ T cell chromatin, as assessed by ATACseq studies. However, 3D chromatin architecture, assessed by HiChIP and simultaneous mapping of CTCF anchors of chromatin loops, reveals that normal 3D chromatin architecture is largely preserved. Overlapping CTCF binding, ATACseq, and RNAseq data with known JIA genetic risk loci demonstrated the presence of genetic influences on the observed transcriptional abnormalities and identified candidate target genes. These studies demonstrate the utility of multi-omics approaches for unraveling important questions regarding the pathobiology of autoimmune diseases.
format	article
author	Evan Tarbell Kaiyu Jiang Teresa R. Hennon Lucy Holmes Sonja Williams Yao Fu Patrick M. Gaffney Tao Liu James N. Jarvis
author_facet	Evan Tarbell Kaiyu Jiang Teresa R. Hennon Lucy Holmes Sonja Williams Yao Fu Patrick M. Gaffney Tao Liu James N. Jarvis
author_sort	Evan Tarbell
title	CD4+ T cells from children with active juvenile idiopathic arthritis show altered chromatin features associated with transcriptional abnormalities
title_short	CD4+ T cells from children with active juvenile idiopathic arthritis show altered chromatin features associated with transcriptional abnormalities
title_full	CD4+ T cells from children with active juvenile idiopathic arthritis show altered chromatin features associated with transcriptional abnormalities
title_fullStr	CD4+ T cells from children with active juvenile idiopathic arthritis show altered chromatin features associated with transcriptional abnormalities
title_full_unstemmed	CD4+ T cells from children with active juvenile idiopathic arthritis show altered chromatin features associated with transcriptional abnormalities
title_sort	cd4+ t cells from children with active juvenile idiopathic arthritis show altered chromatin features associated with transcriptional abnormalities
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0e8fdf375c2a4a7794e76c20764ae53c
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CD4+ T cells from children with active juvenile idiopathic arthritis show altered chromatin features associated with transcriptional abnormalities

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