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Series GSE39081 Query DataSets for GSE39081
Status Public on Oct 03, 2012
Title Genetically-driven target tissue over-expression of CD40: A novel mechanism in autoimmune disease
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary The CD40 gene, an important immune regulatory gene, is also expressed and functional on non-myeloid derived cells, many of which are targets for tissue specific autoimmune diseases, including d thyroid follicular cells in Graves’ disease (GD). Whether target tissue CD40 expression plays a role in autoimmune disease etiology has yet to be determined. Here we show for the first time, that target-tissue over-expression of CD40 plays a key role in the etiology of autoimmunity. Using a murine model of GD, we demonstrated that thyroidal CD40 over-expression augmented the production of thyroid specific antibodies, resulting in more severe experimental autoimmune Graves’ disease (EAGD), whereas deletion of thyroidal CD40 suppressed disease. Using transcriptome and immune-pathway analyses we showed that in both EAGD mouse thyroids and human primary thyrocytes, CD40 mediates this effect by activating downstream cytokines and chemokines, most notably IL-6. To translate these findings into therapy, we blocked IL-6 during EAGD induction in the setting of thyroidal CD40 over-expression, and showed decreased levels of TSHR stimulating antibodies and frequency of disease. We conclude that target tissue over-expression of CD40 plays a key role in the etiology of organ specific autoimmune disease.
Overall design CD40 in Thyroid Autoimmunity: 1) Incubation of human thyroid cells with G28.5, a CD40 stimulating antibody, and purification of RNA, conversion to cDNA, measurement of mRNA expression using RNAseq. 2) Removal of thyroid tissues from CD40 over-expressing transgenic mice and wild type mice, purification of RNA, conversion to cDNA measurement of mRNA expression using RNAseq.
Contributor(s) Huber AK, Finkelman FD, Li CW, Concepcion E, Smith EP, Latif R, Keddache M, Zhang W, Tomer Y
Citation(s) 22888137
Submission date Jul 03, 2012
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)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (6)
GSM955424 Human_T0_RNA_seq
GSM955425 Human_T24_RNA-seq
GSM955426 Mouse_WT_Ctrl_RNA-seq
BioProject PRJNA169916
SRA SRP013984

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE39081_RAW.tar 1.1 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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