Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Type-I interferon response profiling

ABSTRACT: Peripheral blood mononuclear cells were treated with beta-interferon for 2, 6 and 18 hours, and interferon-responsive genes identified. This 'signature' was then analysed in newly diagnosed and long-standing type-1 diabetics, as well as pre-diabetic children and individuals with systemic lupus erythematosus.

ORGANISM(S): Homo sapiens

SUBMITTER: Richard Coulson

PROVIDER: E-MTAB-1724 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

A type I interferon transcriptional signature precedes autoimmunity in children genetically at risk for type 1 diabetes.

Ferreira Ricardo C RC Guo Hui H Coulson Richard M R RM Smyth Deborah J DJ Pekalski Marcin L ML Burren Oliver S OS Cutler Antony J AJ Doecke James D JD Flint Shaun S McKinney Eoin F EF Lyons Paul A PA Smith Kenneth G C KG Achenbach Peter P Beyerlein Andreas A Dunger David B DB Clayton David G DG Wicker Linda S LS Todd John A JA Bonifacio Ezio E Wallace Chris C Ziegler Anette-G AG

Diabetes 20140221 7

Diagnosis of the autoimmune disease type 1 diabetes (T1D) is preceded by the appearance of circulating autoantibodies to pancreatic islets. However, almost nothing is known about events leading to this islet autoimmunity. Previous epidemiological and genetic data have associated viral infections and antiviral type I interferon (IFN) immune response genes with T1D. Here, we first used DNA microarray analysis to identify IFN-β-inducible genes in vitro and then used this set of genes to define an I ...[more]

PMID: 24561305

Similar Datasets

Project description:Polymorphisms in the transcription factor interferon regulatory factor 5 (IRF5) are strongly associated in human genetic studies with an increased risk of developing the autoimmune disease systemic lupus erythematosus. However, the biological role of IRF5 in lupus pathogenesis, if any, is not known. In this study we show that IRF5 is absolutely required for disease development in the FcgRIIB-/-Yaa and FcgRIIB-/- lupus models. In contrast to IRF5-sufficient FcgRIIB-/-Yaa mice, IRF5-deficient FcgRIIB-/-Yaa mice do not develop lupus manifestations and have a phenotype comparable to wildtype mice. Strikingly, full expression of IRF5 is required for the development of autoimmunity, as IRF5-heterozygotes had dramatically reduced disease. One effect of IRF5 is to induce the production of the type I interferon IFN-gamma, a cytokine implicated in lupus pathogenesis. To address the mechanism by which IRF5 promotes disease, we evaluated FcgRIIB-/-Yaa mice lacking the type I interferon receptor IFNAR1. Unlike the IRF5-deficient and IRF5-heterozygous FcgRIIB-/-Yaa mice, IFNAR1-deficient FcgRIIB-/-Yaa mice maintained a substantial level of residual disease. Furthermore, in FcgRIIB-/- mice lacking Yaa, IRF5-deficiency also markedly reduced disease manifestations, indicating that the beneficial effects of IRF5 deficiency in FcgRIIB-/-Yaa mice are not due only to inhibition of the enhanced TLR7 signaling associated with the Yaa mutation. Overall, we demonstrate that IRF5 plays an essential role in lupus pathogenesis in murine models and that this is mediated through pathways beyond that of type I interferon production. The fact that even IRF5 heterozygous mice developed minimal disease makes IRF5 a particularly attractive therapeutic target. Serum samples from a total of 70 mice were run on the Utz Lab Whole Protein Autoantigen Array V1.0 (a single-color platform) in order to profile their autoantibodies against a library of autoimmune antigens. All samples were run once with no replicates. The samples consisted of the following groups: For data appearing in Figure 3D, illustrating that mice lacking IRF5 have their autoantibody levels significantly affected: R2Yaa IRF5+/+: 12 R2Yaa IRF5+/-: 11 R2Yaa IRF5-/-: 14 C57BL/6 ("WT" control): 13 Total mice (arrays) for this group: 50 For data appearing in Figure 6D, illustrating that mice lacking Ifnar1 do not have their autoantibody levels significantly affected: R2Yaa Ifnar+/+: 10 R2Yaa Ifnar-/-: 10 Total mice (arrays) for this group: 20

Dataset Information

Type-I interferon response profiling

Publications

A type I interferon transcriptional signature precedes autoimmunity in children genetically at risk for type 1 diabetes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets