The gene expression profile of CD11c+ CD8α- dendritic cells in the pre-diabetic pancreas of the NOD mouse.

Two major dendritic cell (DC) subsets have been described in the pancreas of mice: The CD11c+ CD8α- DCs (strong CD4+ T cell proliferation inducers) and the CD8α+ CD103+ DCs (T cell apoptosis inducers). Here we analyzed the larger subset of CD11c+ CD8α- DCs isolated from the pancreas of pre-diabetic...

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Autores principales:	Wouter Beumer, Jojanneke M C Welzen-Coppens, Cornelia G van Helden-Meeuwsen, Sinead M Gibney, Hemmo A Drexhage, Marjan A Versnel
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/01a340c3ea124c76ad70e2fa0b32ccb0
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spelling	oai:doaj.org-article:01a340c3ea124c76ad70e2fa0b32ccb02021-11-25T06:02:47ZThe gene expression profile of CD11c+ CD8α- dendritic cells in the pre-diabetic pancreas of the NOD mouse.1932-620310.1371/journal.pone.0103404https://doaj.org/article/01a340c3ea124c76ad70e2fa0b32ccb02014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25166904/?tool=EBIhttps://doaj.org/toc/1932-6203Two major dendritic cell (DC) subsets have been described in the pancreas of mice: The CD11c+ CD8α- DCs (strong CD4+ T cell proliferation inducers) and the CD8α+ CD103+ DCs (T cell apoptosis inducers). Here we analyzed the larger subset of CD11c+ CD8α- DCs isolated from the pancreas of pre-diabetic NOD mice for genome-wide gene expression (validated by Q-PCR) to elucidate abnormalities in underlying gene expression networks. CD11c+ CD8α- DCs were isolated from 5 week old NOD and control C57BL/6 pancreas. The steady state pancreatic NOD CD11c+ CD8α- DCs showed a reduced expression of several gene networks important for the prime functions of these cells, i.e. for cell renewal, immune tolerance induction, migration and for the provision of growth factors including those for beta cell regeneration. A functional in vivo BrdU incorporation test showed the reduced proliferation of steady state pancreatic DC. The reduced expression of tolerance induction genes (CD200R, CCR5 and CD24) was supported on the protein level by flow cytometry. Also previously published functional tests on maturation, immune stimulation and migration confirm the molecular deficits of NOD steady state DC. Despite these deficiencies NOD pancreas CD11c+ CD8α- DCs showed a hyperreactivity to LPS, which resulted in an enhanced pro-inflammatory state characterized by a gene profile of an enhanced expression of a number of classical inflammatory cytokines. The enhanced up-regulation of inflammatory genes was supported by the in vitro cytokine production profile of the DCs. In conclusion, our data show that NOD pancreatic CD11c+ CD8α- DCs show various deficiencies in steady state, while hyperreactive when encountering a danger signal such as LPS.Wouter BeumerJojanneke M C Welzen-CoppensCornelia G van Helden-MeeuwsenSinead M GibneyHemmo A DrexhageMarjan A VersnelPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 8, p e103404 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wouter Beumer Jojanneke M C Welzen-Coppens Cornelia G van Helden-Meeuwsen Sinead M Gibney Hemmo A Drexhage Marjan A Versnel The gene expression profile of CD11c+ CD8α- dendritic cells in the pre-diabetic pancreas of the NOD mouse.
description	Two major dendritic cell (DC) subsets have been described in the pancreas of mice: The CD11c+ CD8α- DCs (strong CD4+ T cell proliferation inducers) and the CD8α+ CD103+ DCs (T cell apoptosis inducers). Here we analyzed the larger subset of CD11c+ CD8α- DCs isolated from the pancreas of pre-diabetic NOD mice for genome-wide gene expression (validated by Q-PCR) to elucidate abnormalities in underlying gene expression networks. CD11c+ CD8α- DCs were isolated from 5 week old NOD and control C57BL/6 pancreas. The steady state pancreatic NOD CD11c+ CD8α- DCs showed a reduced expression of several gene networks important for the prime functions of these cells, i.e. for cell renewal, immune tolerance induction, migration and for the provision of growth factors including those for beta cell regeneration. A functional in vivo BrdU incorporation test showed the reduced proliferation of steady state pancreatic DC. The reduced expression of tolerance induction genes (CD200R, CCR5 and CD24) was supported on the protein level by flow cytometry. Also previously published functional tests on maturation, immune stimulation and migration confirm the molecular deficits of NOD steady state DC. Despite these deficiencies NOD pancreas CD11c+ CD8α- DCs showed a hyperreactivity to LPS, which resulted in an enhanced pro-inflammatory state characterized by a gene profile of an enhanced expression of a number of classical inflammatory cytokines. The enhanced up-regulation of inflammatory genes was supported by the in vitro cytokine production profile of the DCs. In conclusion, our data show that NOD pancreatic CD11c+ CD8α- DCs show various deficiencies in steady state, while hyperreactive when encountering a danger signal such as LPS.
format	article
author	Wouter Beumer Jojanneke M C Welzen-Coppens Cornelia G van Helden-Meeuwsen Sinead M Gibney Hemmo A Drexhage Marjan A Versnel
author_facet	Wouter Beumer Jojanneke M C Welzen-Coppens Cornelia G van Helden-Meeuwsen Sinead M Gibney Hemmo A Drexhage Marjan A Versnel
author_sort	Wouter Beumer
title	The gene expression profile of CD11c+ CD8α- dendritic cells in the pre-diabetic pancreas of the NOD mouse.
title_short	The gene expression profile of CD11c+ CD8α- dendritic cells in the pre-diabetic pancreas of the NOD mouse.
title_full	The gene expression profile of CD11c+ CD8α- dendritic cells in the pre-diabetic pancreas of the NOD mouse.
title_fullStr	The gene expression profile of CD11c+ CD8α- dendritic cells in the pre-diabetic pancreas of the NOD mouse.
title_full_unstemmed	The gene expression profile of CD11c+ CD8α- dendritic cells in the pre-diabetic pancreas of the NOD mouse.
title_sort	gene expression profile of cd11c+ cd8α- dendritic cells in the pre-diabetic pancreas of the nod mouse.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/01a340c3ea124c76ad70e2fa0b32ccb0
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The gene expression profile of CD11c+ CD8α- dendritic cells in the pre-diabetic pancreas of the NOD mouse.

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