The transcriptional response of mouse spleen B cells to IL-4: Comparison to the response of human peripheral blood B cells
The Th2 cytokine IL-4 triggers a signaling cascade which activates transcription by STAT6. The goals of the present study are to define the transcriptomic response of mouse spleen B cells (mSBC) to IL-4 used as single stimulus, its specificity compared to human peripheral blood B cells (hPBBC) and t...
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doaj-2addb309816d480abaf66d670fc240402020-11-24T20:49:15ZengElsevierBiochemistry and Biophysics Reports2405-58082018-12-01165661The transcriptional response of mouse spleen B cells to IL-4: Comparison to the response of human peripheral blood B cellsNatalia Ruiz-Lafuente0Manuel Muro1Alfredo Minguela2Antonio Parrado3Servicio de Inmunología, Hospital Clínico Universitario Virgen de la Arrixaca, Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), El Palmar, 30120 Murcia, SpainServicio de Inmunología, Hospital Clínico Universitario Virgen de la Arrixaca, Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), El Palmar, 30120 Murcia, SpainServicio de Inmunología, Hospital Clínico Universitario Virgen de la Arrixaca, Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), El Palmar, 30120 Murcia, SpainCorresponding author.; Servicio de Inmunología, Hospital Clínico Universitario Virgen de la Arrixaca, Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), El Palmar, 30120 Murcia, SpainThe Th2 cytokine IL-4 triggers a signaling cascade which activates transcription by STAT6. The goals of the present study are to define the transcriptomic response of mouse spleen B cells (mSBC) to IL-4 used as single stimulus, its specificity compared to human peripheral blood B cells (hPBBC) and to mouse spleen T cells (mSTC), and the pathways affected. Oligonucleotide-based microarrays were performed using two references, the untreated sample and the cells cultured without IL-4, an experimental design which reduces the potential confounding effect of cellular stress during culture. Specificity was addressed by comparing the response of mSBC and our previously published study on hPBBC, of similar design, and a study by other authors on mSTC. We detected an mSBC-specific response (including novel genes, e.g., Sertad4, Lifr, Pmepa1, Epcam, Tbxas1; and common genes, e.g., Usp2, Cst7, Grtp1, and Casp6), an hPBBC-specific response (e.g., CCL17, MTCL1, GCSAM, HOMER2, IL2RA), and a common mSBC/hPBBC response (e.g., CISH, NFIL3, SOCS1, VDR, CDH1). In contrast, the mSBC and mSTC responses were largely divergent. Gene set enrichment analysis (GSEA) was applied for the first time to identify the pathways affected. Both in mSBC and hPBBC, IL-4 activated Myc, the transcriptional machinery itself, cell cycle, mitochondria and respiratory chain, ribosome, proteasome and antigen presentation, and Wnt signaling, and inhibited GPCR signaling. However, significant differences were found in histone demethylation, Nod signaling, and Rho signaling, which were downregulated in mSBC, and in chromatin condensation, which was downregulated in hPBBC. These findings may have therapeutic implications for the treatment of allergic diseases and parasitic infections. Keywords: IL-4, B cells, Microarray, GSEA, Mitochondria, Wnt signalinghttp://www.sciencedirect.com/science/article/pii/S2405580818301183 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Natalia Ruiz-Lafuente Manuel Muro Alfredo Minguela Antonio Parrado |
spellingShingle |
Natalia Ruiz-Lafuente Manuel Muro Alfredo Minguela Antonio Parrado The transcriptional response of mouse spleen B cells to IL-4: Comparison to the response of human peripheral blood B cells Biochemistry and Biophysics Reports |
author_facet |
Natalia Ruiz-Lafuente Manuel Muro Alfredo Minguela Antonio Parrado |
author_sort |
Natalia Ruiz-Lafuente |
title |
The transcriptional response of mouse spleen B cells to IL-4: Comparison to the response of human peripheral blood B cells |
title_short |
The transcriptional response of mouse spleen B cells to IL-4: Comparison to the response of human peripheral blood B cells |
title_full |
The transcriptional response of mouse spleen B cells to IL-4: Comparison to the response of human peripheral blood B cells |
title_fullStr |
The transcriptional response of mouse spleen B cells to IL-4: Comparison to the response of human peripheral blood B cells |
title_full_unstemmed |
The transcriptional response of mouse spleen B cells to IL-4: Comparison to the response of human peripheral blood B cells |
title_sort |
transcriptional response of mouse spleen b cells to il-4: comparison to the response of human peripheral blood b cells |
publisher |
Elsevier |
series |
Biochemistry and Biophysics Reports |
issn |
2405-5808 |
publishDate |
2018-12-01 |
description |
The Th2 cytokine IL-4 triggers a signaling cascade which activates transcription by STAT6. The goals of the present study are to define the transcriptomic response of mouse spleen B cells (mSBC) to IL-4 used as single stimulus, its specificity compared to human peripheral blood B cells (hPBBC) and to mouse spleen T cells (mSTC), and the pathways affected. Oligonucleotide-based microarrays were performed using two references, the untreated sample and the cells cultured without IL-4, an experimental design which reduces the potential confounding effect of cellular stress during culture. Specificity was addressed by comparing the response of mSBC and our previously published study on hPBBC, of similar design, and a study by other authors on mSTC. We detected an mSBC-specific response (including novel genes, e.g., Sertad4, Lifr, Pmepa1, Epcam, Tbxas1; and common genes, e.g., Usp2, Cst7, Grtp1, and Casp6), an hPBBC-specific response (e.g., CCL17, MTCL1, GCSAM, HOMER2, IL2RA), and a common mSBC/hPBBC response (e.g., CISH, NFIL3, SOCS1, VDR, CDH1). In contrast, the mSBC and mSTC responses were largely divergent. Gene set enrichment analysis (GSEA) was applied for the first time to identify the pathways affected. Both in mSBC and hPBBC, IL-4 activated Myc, the transcriptional machinery itself, cell cycle, mitochondria and respiratory chain, ribosome, proteasome and antigen presentation, and Wnt signaling, and inhibited GPCR signaling. However, significant differences were found in histone demethylation, Nod signaling, and Rho signaling, which were downregulated in mSBC, and in chromatin condensation, which was downregulated in hPBBC. These findings may have therapeutic implications for the treatment of allergic diseases and parasitic infections. Keywords: IL-4, B cells, Microarray, GSEA, Mitochondria, Wnt signaling |
url |
http://www.sciencedirect.com/science/article/pii/S2405580818301183 |
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