Ulcerative colitis immune cell landscapes and differentially expressed gene signatures determine novel regulators and predict clinical response to biologic therapy

Abstract The heterogeneous pathobiology underlying Ulcerative Colitis (UC) is not fully understood. Using publicly available transcriptomes from adult UC patients, we identified the immune cell landscape, molecular pathways, and differentially expressed genes (DEGs) across patient cohorts and their...

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Autores principales:	Harrison M. Penrose, Rida Iftikhar, Morgan E. Collins, Eman Toraih, Emmanuelle Ruiz, Nathan Ungerleider, Hani Nakhoul, Erik F. Flemington, Emad Kandil, Shamita B. Shah, Suzana D. Savkovic
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e760a94f0fe148a6a82d2a1f02490469
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spelling	oai:doaj.org-article:e760a94f0fe148a6a82d2a1f024904692021-12-02T13:41:43ZUlcerative colitis immune cell landscapes and differentially expressed gene signatures determine novel regulators and predict clinical response to biologic therapy10.1038/s41598-021-88489-w2045-2322https://doaj.org/article/e760a94f0fe148a6a82d2a1f024904692021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88489-whttps://doaj.org/toc/2045-2322Abstract The heterogeneous pathobiology underlying Ulcerative Colitis (UC) is not fully understood. Using publicly available transcriptomes from adult UC patients, we identified the immune cell landscape, molecular pathways, and differentially expressed genes (DEGs) across patient cohorts and their association with treatment outcomes. The global immune cell landscape of UC tissue included increased neutrophils, T CD4 memory activated cells, active dendritic cells (DC), and M0 macrophages, as well as reduced trends in T CD8, Tregs, B memory, resting DC, and M2 macrophages. Pathway analysis of DEGs across UC cohorts demonstrated activated bacterial, inflammatory, growth, and cellular signaling. We identified a specific transcriptional signature of one hundred DEGs (UC100) that distinctly separated UC inflamed from uninflamed transcriptomes. Several UC100 DEGs, with unidentified roles in UC, were validated in primary tissue. Additionally, non-responders to anti-TNFα and anti-α4β7 therapy displayed distinct profiles of immune cells and pathways pertaining to inflammation, growth, and metabolism. We identified twenty resistant DEGs in UC non-responders to both therapies of which four had significant predictive power to treatment outcome. We demonstrated the global immune landscape and pathways in UC tissue, highlighting a unique UC signature across cohorts and a UC resistant signature with predictive performance to biologic therapy outcome.Harrison M. PenroseRida IftikharMorgan E. CollinsEman ToraihEmmanuelle RuizNathan UngerleiderHani NakhoulErik F. FlemingtonEmad KandilShamita B. ShahSuzana D. SavkovicNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Harrison M. Penrose Rida Iftikhar Morgan E. Collins Eman Toraih Emmanuelle Ruiz Nathan Ungerleider Hani Nakhoul Erik F. Flemington Emad Kandil Shamita B. Shah Suzana D. Savkovic Ulcerative colitis immune cell landscapes and differentially expressed gene signatures determine novel regulators and predict clinical response to biologic therapy
description	Abstract The heterogeneous pathobiology underlying Ulcerative Colitis (UC) is not fully understood. Using publicly available transcriptomes from adult UC patients, we identified the immune cell landscape, molecular pathways, and differentially expressed genes (DEGs) across patient cohorts and their association with treatment outcomes. The global immune cell landscape of UC tissue included increased neutrophils, T CD4 memory activated cells, active dendritic cells (DC), and M0 macrophages, as well as reduced trends in T CD8, Tregs, B memory, resting DC, and M2 macrophages. Pathway analysis of DEGs across UC cohorts demonstrated activated bacterial, inflammatory, growth, and cellular signaling. We identified a specific transcriptional signature of one hundred DEGs (UC100) that distinctly separated UC inflamed from uninflamed transcriptomes. Several UC100 DEGs, with unidentified roles in UC, were validated in primary tissue. Additionally, non-responders to anti-TNFα and anti-α4β7 therapy displayed distinct profiles of immune cells and pathways pertaining to inflammation, growth, and metabolism. We identified twenty resistant DEGs in UC non-responders to both therapies of which four had significant predictive power to treatment outcome. We demonstrated the global immune landscape and pathways in UC tissue, highlighting a unique UC signature across cohorts and a UC resistant signature with predictive performance to biologic therapy outcome.
format	article
author	Harrison M. Penrose Rida Iftikhar Morgan E. Collins Eman Toraih Emmanuelle Ruiz Nathan Ungerleider Hani Nakhoul Erik F. Flemington Emad Kandil Shamita B. Shah Suzana D. Savkovic
author_facet	Harrison M. Penrose Rida Iftikhar Morgan E. Collins Eman Toraih Emmanuelle Ruiz Nathan Ungerleider Hani Nakhoul Erik F. Flemington Emad Kandil Shamita B. Shah Suzana D. Savkovic
author_sort	Harrison M. Penrose
title	Ulcerative colitis immune cell landscapes and differentially expressed gene signatures determine novel regulators and predict clinical response to biologic therapy
title_short	Ulcerative colitis immune cell landscapes and differentially expressed gene signatures determine novel regulators and predict clinical response to biologic therapy
title_full	Ulcerative colitis immune cell landscapes and differentially expressed gene signatures determine novel regulators and predict clinical response to biologic therapy
title_fullStr	Ulcerative colitis immune cell landscapes and differentially expressed gene signatures determine novel regulators and predict clinical response to biologic therapy
title_full_unstemmed	Ulcerative colitis immune cell landscapes and differentially expressed gene signatures determine novel regulators and predict clinical response to biologic therapy
title_sort	ulcerative colitis immune cell landscapes and differentially expressed gene signatures determine novel regulators and predict clinical response to biologic therapy
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e760a94f0fe148a6a82d2a1f02490469
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Ulcerative colitis immune cell landscapes and differentially expressed gene signatures determine novel regulators and predict clinical response to biologic therapy

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