Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human FoxP3+CD4+CD25+high regulatory T cells (Tregs) isolated from recent-onset type 1 diabetes mellitus (T1D) patients and controls


ABSTRACT: Naturally occurring FoxP3+CD4+CD25+high regulatory T cells (Tregs) play an important role in dominant tolerance, suppressing auto-reactive CD4+CD25- T cell activity. Although Tregs from T1D subjects are functionally deficient, there is little knowledge of the molecular mechanisms that orchestrate this loss of Treg function. We observed increased apoptosis (by a novel YOPRO-1/7AAD dual staining protocol) and decreased suppression in polyclonal Tregs in the periphery from high at-risk and T1D subjects. We hypothesize that prior to and during the onset of disease, Tregs lack pro-survival signals and are caught up in a relatively deficient cytokine milieu whose effects may be detectable in the periphery. Microarray analysis was performed on un-stimulated Tregs from 12 subjects with newly diagnosed T1D and 15 healthy controls. Experiment Overall Design: Recent-onset T1D subjects were T1D patients diagnosed within 1 year. At the time of each visit, the following clinical measurements were taken: HbA1c, glucose level, height, weight and BMI. The presence of auto-antibodies was measured from peripheral blood. Peripheral blood mononuclear cells (PBMCs) were collected and Tregs were isolated using FACS isolation. RNA was isolated, amplified and cRNA was fragmented and hybridized to Affymetrix whole genome U133Plus2.0 arrays having 54675 probe-sets. Bayesian Hierarchical analysis (BGX) was used to analyze the data.

ORGANISM(S): Homo sapiens

SUBMITTER: Parthav Jailwala 

PROVIDER: E-GEOD-10586 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Apoptosis of CD4+ CD25(high) T cells in type 1 diabetes may be partially mediated by IL-2 deprivation.

Jailwala Parthav P   Waukau Jill J   Glisic Sanja S   Jana Srikanta S   Ehlenbach Sarah S   Hessner Martin M   Alemzadeh Ramin R   Matsuyama Shigemi S   Laud Purushottam P   Wang Xujing X   Ghosh Soumitra S  

PloS one 20090805 8


<h4>Background</h4>Type 1 diabetes (T1D) is a T-cell mediated autoimmune disease targeting the insulin-producing pancreatic beta cells. Naturally occurring FOXP3(+)CD4(+)CD25(high) regulatory T cells (T(regs)) play an important role in dominant tolerance, suppressing autoreactive CD4(+) effector T cell activity. Previously, in both recent-onset T1D patients and beta cell antibody-positive at-risk individuals, we observed increased apoptosis and decreased function of polyclonal T(regs) in the per  ...[more]

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