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Inhalation of panaxadiol alleviates lung inflammation via inhibiting TNFA/TNFAR and IL7/IL7R signalling

ABSTRACT: Inhalation of panaxadiol alleviates lung inflammation via inhibiting TNFA/TNFAR and IL7/IL7R signalling

PROVIDER: PRJNA943212 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23734233_1.fastq.gz	Fastqsanger.gz
	SRR23734233_2.fastq.gz	Fastqsanger.gz
	SRR23734234_1.fastq.gz	Fastqsanger.gz
	SRR23734234_2.fastq.gz	Fastqsanger.gz
	SRR23734235_1.fastq.gz	Fastqsanger.gz

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Project description:Genome-wide association studies in multiple sclerosis (MS) identified a polymorphism (rs6897932) located in the coding region of the alpha chain of the cytokine receptor interleukin 7 receptor (IL7R) as a component that increases susceptibility to develop the disease. This single nucleotide polymorphism (SNP) affects the splicing of the primary transcript leading to genotype-defined transcript ratios encoding either a full length membrane spanning form or a soluble receptor chain. Genotyping at the IL7R locus reveals that the region can be described by four haplotypes. Interestingly, only one out of three haplotypes harbouring the associated SNP is positively associated with MS whereas the other two do not show association. The minor allele containing haplotype shows a reduced susceptibility to develop MS. We hypothesized that additional functional or phenotypic differences exist between individuals homozygous for haplotypes shown to have either positive, negative, or neutral effect, on susceptibility to develop MS. Gene expression profiles of CD4+ T cells from MS individuals before and after stimulation with IL7 were recorded. Haplotype-specific gene signatures were found indicating small alterations in IL7/IL7R signal processing/sensitivity through JAK/STAT and p38/MAPK14. We can not exclude that the obtained signatures result from differences within the CD4+ T cell compartment that, in fact, should be seen as a consequence of systemic haplotype-specific processing of homeostatic and proliferation signals transmitted through IL7/IL7R. Samples of CD4+ cells were obtained from 7 MS patients (homozygous for Hap1 (3), Hap2 (2), Hap3 (2)). CD4+ cells were collected from peripheral blood, frozen and stored in liquid nitrogen. All samples were thawed and CD4+ cells were purified by magnetic bead separation. Purity and viability of cells was analyzed by Fluorescence Activated Cell Sorter (FACS). Total cellular RNA were extracted with TRIzol reagent and analyzed with the Human Gene 1.0 ST Array (affymetrix). IL7R haplotypes and susceptibility to develop MS: Hap1 homozygous <-> Risk <-> positive effect on MS susceptibility Hap2 homozygous <-> Hap2 <-> neutral effect on MS susceptibility Hap3 homozygous <-> Prot <-> neutral effect on MS susceptibility [Note: Haplotype nomenclature subject to revision.]

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Inhalation of panaxadiol alleviates lung inflammation via inhibiting TNFA/TNFAR and IL7/IL7R signalling

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