Linked Life Data

21287555

Source:http://linkedlifedata.com/resource/pubmed/id/21287555

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-2-22
pubmed:abstractText
Treg homeostasis is disturbed in multiple sclerosis (MS). Frequencies of recent thymic emigrant (RTE)-Treg are reduced and the disparity between RTE-Treg and long-lived memory Treg coincides with the MS-associated Treg defect, as shown previously. Recent studies demonstrate that IL-7 and thymic stromal lymphopoietin (TSLP) are critical for Treg maturation. Therefore, altered signaling through their receptors (IL-7R, TSLP receptor (TSLPR)), sharing the IL-7R?-chain (IL-7R?), might contribute to impaired Treg development. Using blood samples from 56 patients with MS and 33 healthy controls, we assessed IL-7R?-expression on conventional T cells; frequencies, phenotypes and suppressive activities of Treg, plasma levels of IL-7 and soluble IL-7R?; and screened for MS-associated IL-7RA gene polymorphism rs6897932. Moreover, we determined Treg expressing two different TCR V?-chains designating thymus-originated cells. As TSLP/TSLPR signaling in thymic myeloid dendritic cells (MDCs) promotes Treg differentiation, we measured TSLPR expression on peripheral MDCs to indirectly test whether altered TSLPR expression might add to compromised Treg neogenesis. We found reduced IL-7R? expression on conventional T cells and upregulated IL-7 plasma levels together with reduction of RTE-Treg frequencies and Treg function in MS, without clear genetic influence. Decreased IL-7R? expression in MS correlated with declined dual-receptor-Treg and reduced MDC TSLPR expression, indicating contracted thymic Treg output. We suggest that altered IL-7R/TSLPR signaling contributes to impaired Treg neogenesis in MS, which is compensated by expanded memory-Treg and finally results in dysfunctional Treg.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1521-4141
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
pubmed:issnType
Electronic
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
845-53
pubmed:meshHeading
pubmed-meshheading:21287555-Adolescent, pubmed-meshheading:21287555-Adult, pubmed-meshheading:21287555-Aged, pubmed-meshheading:21287555-CD4-Positive T-Lymphocytes, pubmed-meshheading:21287555-Case-Control Studies, pubmed-meshheading:21287555-Child, pubmed-meshheading:21287555-Cytokines, pubmed-meshheading:21287555-Dendritic Cells, pubmed-meshheading:21287555-Female, pubmed-meshheading:21287555-Homeostasis, pubmed-meshheading:21287555-Humans, pubmed-meshheading:21287555-Interleukin-7, pubmed-meshheading:21287555-Male, pubmed-meshheading:21287555-Middle Aged, pubmed-meshheading:21287555-Multiple Sclerosis, pubmed-meshheading:21287555-Polymorphism, Single Nucleotide, pubmed-meshheading:21287555-Receptors, Antigen, T-Cell, alpha-beta, pubmed-meshheading:21287555-Receptors, Cytokine, pubmed-meshheading:21287555-Receptors, Interleukin-7, pubmed-meshheading:21287555-Signal Transduction, pubmed-meshheading:21287555-T-Lymphocytes, Regulatory, pubmed-meshheading:21287555-Young Adult
pubmed:year
2011
pubmed:articleTitle
The interleukin-7 receptor ? chain contributes to altered homeostasis of regulatory T cells in multiple sclerosis.
pubmed:affiliation
Division of Molecular Neuroimmunology, Department of Neurology, University Hospital of Heidelberg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't