Microarray detection of E2F pathway activation and other targets in multiple sclerosis peripheral blood mononuclear cells.
We performed microarray analysis of peripheral blood mononuclear cells (PBMCs) from multiple sclerosis (MS) patients and detected a profile of immune cell activation, autoantigen upregulation, and enhanced E2F pathway transcription. Accordingly, E2f1-deficient mice manifested only mild disability upon induction of experimental autoimmune encephalomyelitis (EAE). Furthermore, PBMCs from Avonex-treated patients had lower expression of E2F targets. The profile was enriched in genes known to harbor MS-associated polymorphisms, or localized to MS susceptibility chromosomal regions. Our study shows that PBMC microarrays reflect MS pathobiology that can be validated in the EAE model.
Iglesias
Antonio H
AH
Laboratory of Transcriptional and Immune Regulation, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02139, USA.
Camelo
Sandra
S
Hwang
Daehee
D
Villanueva
Raul
R
Stephanopoulos
George
G
Dangond
Fernando
F
D000293:Adolescent; D000328:Adult; D000818:Animals; D018797:Cell Cycle Proteins; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods / Q000706:statistics & numerical data; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D005810:Multigene Family / Q000187:drug effects; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods / Q000706:statistics & numerical data; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C493754:E2f1 protein, mouse; D014157:Transcription Factors; D016899:Interferon-beta; D000068556:Interferon beta-1a