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Lymphocyte Activation Dynamics Is Shaped by Hereditary Components at Chromosome Region 17q12-q21

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dc.contributor.author Carreras Sureda, Amado, 1986-
dc.contributor.author Rubio Moscardó, Fanny
dc.contributor.author Olvera, Alex
dc.contributor.author Argilaguet Marqués, Jordi, 1977-
dc.contributor.author Kiefer, Kerstin, 1986-
dc.contributor.author Mothe, Beatriz
dc.contributor.author Meyerhans, Andreas
dc.contributor.author Brander, Christian
dc.contributor.author Vicente García, Rubén, 1978-
dc.date.accessioned 2017-03-08T13:03:57Z
dc.date.available 2017-03-08T13:03:57Z
dc.date.issued 2016
dc.identifier.citation Carreras Sureda A, Rubio Moscardó F, Olvera A, Argilaguet J, Kiefer K, Mothe B, Meyerhans A, Brander C, Vicente García R. Lymphocyte Activation Dynamics Is Shaped by Hereditary Components at Chromosome Region 17q12-q21. PLoS ONE. 2016; 11(11): e0166414. DOI: 10.1371/journal.pone.0166414
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/10230/28187
dc.description.abstract Single nucleotide polymorphisms (SNPs) located in the chromosome region 17q12-q21 are risk factors for asthma. Particularly, there are cis-regulatory haplotypes within this region that regulate differentially the expression levels of ORMDL3, GSDMB and ZPBP2 genes. Remarkably, ORMDL3 has been shown to modulate lymphocyte activation parameters in a heterologous expression system. In this context, it has been shown that Th2 and Th17 cytokine production is affected by SNPs in this region. Therefore, we aim to assess the impact of hereditary components within region 17q12-q21 on the activation profile of human T lymphocytes, focusing on the haplotype formed by allelic variants of SNPs rs7216389 and rs12936231. We measured calcium influx and activation markers, as well as the proliferation rate upon T cell activation. Haplotype-dependent differences in mRNA expression levels of IL-2 and INF-γ were observed at early times after activation. In addition, the allelic variants of these SNPs impacted on the extent of calcium influx in resting lymphocytes and altered proliferation rates in a dose dependent manner. As a result, the asthma risk haplotype carriers showed a lower threshold of saturation during activation. Finally, we confirmed differences in activation marker expression by flow cytometry using phytohemagglutinin, a strong polyclonal stimulus. Altogether, our data suggest that the genetic component of pro-inflammatory pathologies present in this chromosome region could be explained by different T lymphocyte activation dynamics depending on individual allelic heredity.
dc.description.sponsorship This work was supported by grants from the Spanish Ministry of Economy and Competitiveness (SAF2010-16725, SAF2013-46077-R, SAF2014-52228-R, BES-2011-043839), Fondo de Investigación Sanitaria (Red HERACLES RD12/0042/0014), Fundació la Marató de TV3 (20134030) and Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT 3150113). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Public Library of Science (PLoS)
dc.relation.ispartof PLoS ONE. 2016; 11(11): e0166414
dc.rights © 2016 Carreras-Sureda et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.rights.uri https://creativecommons.org/licenses/by/4.0/
dc.title Lymphocyte Activation Dynamics Is Shaped by Hereditary Components at Chromosome Region 17q12-q21
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0166414
dc.subject.keyword Haplotypes
dc.subject.keyword T cells
dc.subject.keyword Gene expression
dc.subject.keyword Lymphocytes
dc.subject.keyword Asthma
dc.subject.keyword Chromosomes
dc.subject.keyword Flow cytometry
dc.subject.keyword T cell receptors
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2010-16725
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2013-46077-R
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2014-52228-R
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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