Altered expression of genes controlling metabolism characterizes the tissue response to immune injury in lupus

Abstract To compare lupus pathogenesis in disparate tissues, we analyzed gene expression profiles of human discoid lupus erythematosus (DLE) and lupus nephritis (LN). We found common increases in myeloid cell-defining gene sets and decreases in genes controlling glucose and lipid metabolism in lupus...

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Autores principales:	Kathryn M. Kingsmore, Prathyusha Bachali, Michelle D. Catalina, Andrea R. Daamen, Sarah E. Heuer, Robert D. Robl, Amrie C. Grammer, Peter E. Lipsky
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9cae1bbe0654450f8dbce0fa0083bd35
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spelling	oai:doaj.org-article:9cae1bbe0654450f8dbce0fa0083bd352021-12-02T16:50:24ZAltered expression of genes controlling metabolism characterizes the tissue response to immune injury in lupus10.1038/s41598-021-93034-w2045-2322https://doaj.org/article/9cae1bbe0654450f8dbce0fa0083bd352021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93034-whttps://doaj.org/toc/2045-2322Abstract To compare lupus pathogenesis in disparate tissues, we analyzed gene expression profiles of human discoid lupus erythematosus (DLE) and lupus nephritis (LN). We found common increases in myeloid cell-defining gene sets and decreases in genes controlling glucose and lipid metabolism in lupus-affected skin and kidney. Regression models in DLE indicated increased glycolysis was correlated with keratinocyte, endothelial, and inflammatory cell transcripts, and decreased tricarboxylic (TCA) cycle genes were correlated with the keratinocyte signature. In LN, regression models demonstrated decreased glycolysis and TCA cycle genes were correlated with increased endothelial or decreased kidney cell transcripts, respectively. Less severe glomerular LN exhibited similar alterations in metabolism and tissue cell transcripts before monocyte/myeloid cell infiltration in some patients. Additionally, changes to mitochondrial and peroxisomal transcripts were associated with specific cells rather than global signal changes. Examination of murine LN gene expression demonstrated metabolic changes were not driven by acute exposure to type I interferon and could be restored after immunosuppression. Finally, expression of HAVCR1, a tubule damage marker, was negatively correlated with the TCA cycle signature in LN models. These results indicate that altered metabolic dysfunction is a common, reversible change in lupus-affected tissues and appears to reflect damage downstream of immunologic processes.Kathryn M. KingsmorePrathyusha BachaliMichelle D. CatalinaAndrea R. DaamenSarah E. HeuerRobert D. RoblAmrie C. GrammerPeter E. LipskyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kathryn M. Kingsmore Prathyusha Bachali Michelle D. Catalina Andrea R. Daamen Sarah E. Heuer Robert D. Robl Amrie C. Grammer Peter E. Lipsky Altered expression of genes controlling metabolism characterizes the tissue response to immune injury in lupus
description	Abstract To compare lupus pathogenesis in disparate tissues, we analyzed gene expression profiles of human discoid lupus erythematosus (DLE) and lupus nephritis (LN). We found common increases in myeloid cell-defining gene sets and decreases in genes controlling glucose and lipid metabolism in lupus-affected skin and kidney. Regression models in DLE indicated increased glycolysis was correlated with keratinocyte, endothelial, and inflammatory cell transcripts, and decreased tricarboxylic (TCA) cycle genes were correlated with the keratinocyte signature. In LN, regression models demonstrated decreased glycolysis and TCA cycle genes were correlated with increased endothelial or decreased kidney cell transcripts, respectively. Less severe glomerular LN exhibited similar alterations in metabolism and tissue cell transcripts before monocyte/myeloid cell infiltration in some patients. Additionally, changes to mitochondrial and peroxisomal transcripts were associated with specific cells rather than global signal changes. Examination of murine LN gene expression demonstrated metabolic changes were not driven by acute exposure to type I interferon and could be restored after immunosuppression. Finally, expression of HAVCR1, a tubule damage marker, was negatively correlated with the TCA cycle signature in LN models. These results indicate that altered metabolic dysfunction is a common, reversible change in lupus-affected tissues and appears to reflect damage downstream of immunologic processes.
format	article
author	Kathryn M. Kingsmore Prathyusha Bachali Michelle D. Catalina Andrea R. Daamen Sarah E. Heuer Robert D. Robl Amrie C. Grammer Peter E. Lipsky
author_facet	Kathryn M. Kingsmore Prathyusha Bachali Michelle D. Catalina Andrea R. Daamen Sarah E. Heuer Robert D. Robl Amrie C. Grammer Peter E. Lipsky
author_sort	Kathryn M. Kingsmore
title	Altered expression of genes controlling metabolism characterizes the tissue response to immune injury in lupus
title_short	Altered expression of genes controlling metabolism characterizes the tissue response to immune injury in lupus
title_full	Altered expression of genes controlling metabolism characterizes the tissue response to immune injury in lupus
title_fullStr	Altered expression of genes controlling metabolism characterizes the tissue response to immune injury in lupus
title_full_unstemmed	Altered expression of genes controlling metabolism characterizes the tissue response to immune injury in lupus
title_sort	altered expression of genes controlling metabolism characterizes the tissue response to immune injury in lupus
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9cae1bbe0654450f8dbce0fa0083bd35
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Altered expression of genes controlling metabolism characterizes the tissue response to immune injury in lupus

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