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Series GSE25115 Query DataSets for GSE25115
Status Public on Nov 03, 2011
Title Interferon-alpha mediates the development of autoimmunity by direct tissue toxicity and through immune-cell recruitment mechanisms
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Interferon-alpha is a major therapeutic agent for many diverse diseases. However, the interferon-alpha mechanism of therapeutic action and associated side effects are not well understood. In particular, thyroiditis is a common unexplained complication. We hypothesized that direct thyroid-toxic actions coupled with immune mechanisms play a major role in the thyroiditis etiology. To test this hypothesis, we investigated the actions of interferon-alpha on cultured thyrocytes in vitro, and in vivo by creating transgenic mice overexpressing interferon-alpha tissue specifically in thyrocytes. Interferon-alpha treatment of cultured PCCL3 rat thyrocytes increased markers of thyroid differentiation, levels of MHC class I, and expression of heat shock protein and CXCL10. This was associated with markedly increased nonapoptotic thyroid cell death. Consistent with these in vitro findings, transgenic mice overexpressing interferon-alpha in the thyroid displayed striking thyroid cell death characteristic of nonimmune thyroid destruction that progressed to profound primary hypothyroidism. Moreover, genes linked to cell death pathways, granzyme B, or known to be associated with recruitment of a cytotoxic immune response, CXCL10, interleukin-23, and TRIM21 were increased in the transgenic thyroids. Taken together, the etiology of interferon-induced thyroiditis likely involves both a direct toxic action on thyrocytes, as well as provocation of a destructive immune response.
Overall design 1) Thyroid cells were incubated with interferon-alpha, and global gene expression was determined by RNA-seq. 2) Thyroid tissues were obtained from transgenic mice overexpressing interferon-alpha and from wild type mice, and global gene expression was analyzed using RNA-seq.
Contributor(s) Akeno N, Smith EP, Huber AK, Stefan M, Zhang W, Keddache M, Tomer Y
Citation(s) 21402899
Submission date Nov 03, 2010
Last update date May 15, 2019
Contact name Weijia Zhang
Phone 212-241-2883
Organization name Mount Sinai School of Medicine
Department Department of Medicine
Lab Bioinformatics Lab
Street address 1425 Madison Avenue
City New York
State/province NY
ZIP/Postal code 10029
Country USA
Platforms (2)
GPL10999 Illumina Genome Analyzer IIx (Homo sapiens)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
Samples (5)
GSM652438 human_T0_RNA-seq
GSM652439 human_T12_RNA-seq
GSM652440 human_T24_RNA-seq
SRA SRP005396
BioProject PRJNA134511

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Supplementary file Size Download File type/resource
GSE25115_RAW.tar 120.8 Mb (http)(custom) TAR (of BED, TXT)
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Raw data are available in SRA
Processed data included within Sample table
Processed data provided as supplementary file

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