title: IL7RA haplotype-associated alterations in cellular immune function and gene expression patterns in multiple sclerosis.
abstract: Interleukin-7 receptor alpha (IL7RA) is among the top listed candidate genes influencing the risk to develop multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system. Soluble IL-7RA (sIL-7RA) protein and mRNA levels vary among the four common IL7RA haplotypes. Here we show and confirm that protective haplotype carriers have three times lower sIL-7RA serum levels than the other three haplotypes. High sIL-7RA concentrations significantly decrease IL-7-mediated STAT5 phosphorylation in CD4(+) T cells. Transcriptome analysis of unstimulated and stimulated CD4(+) T cells of MS patients carrying the different IL7RA haplotypes revealed complex and overlapping patterns in genes participating in cytokine signaling networks, apoptosis, cell cycle progression and cell differentiation. Our findings indicate that genetic variants of IL7RA result in haplotype-associated differential responsiveness to immunological stimuli that influence MS susceptibility not exclusively by varying levels of sIL-7RA.
authors.affiliation: Institute for Neuroimmunology and Clinical Multiple Sclerosis Research (inims), Centre for Molecular Neurobiology Hamburg (ZMNH), University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Jäger
authors.forename: C
authors.initials: C
authors.lastname: Schulze
authors.forename: S
authors.initials: S
authors.lastname: Rösner
authors.forename: R
authors.initials: R
authors.lastname: Martin
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D005260:Female; D053263:Gene Regulatory Networks; D006239:Haplotypes; D006801:Humans; D053699:Interleukin-7 Receptor alpha Subunit / Q000235:genetics* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology; D010766:Phosphorylation; D020641:Polymorphism, Single Nucleotide; D050799:STAT5 Transcription Factor / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D053699:Interleukin-7 Receptor alpha Subunit; D050799:STAT5 Transcription Factor