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IL-7/IL-7R gene variants impact circulating IL-7/IL-7R homeostasis and ART-associated immune recovery status.

ABSTRACT: A relationship between polymorphisms in genes encoding interleukin 7 (IL-7) and its cellular receptor (IL-7R) and antiretroviral therapy (ART)-associated immune recovery in HIV subjects has been previously reported. However, details of this relationship remain unclear, and the association of these polymorphisms with circulating IL-7/IL-7R levels is scarce. Here, we explored whether IL-7/IL-7R axis was associated with quantitative CD4⁺ T-cell recovery in HIV-infected subjects. IL-7/IL-7R polymorphisms were assessed by genotyping, and multiple inheritance models were used to estimate both, their association with low pre-ART CD4⁺ T-cell counts and incomplete immune recovery status after 48 weeks of suppressive ART. Integrated data from genetic variants association and soluble plasma IL-7/IL-7R quantification suggest that IL-7/IL-7R genotype expression could alter the homeostatic balance between soluble and membrane-bound receptors. The haplotype analyses indicates that allele combinations impacts pre-ART circulating CD4⁺ T-cell counts, immune recovery status and the absolute increment of CD4⁺ T-cell counts. The knowledge about how IL-7/IL-7R axis is related to quantitative CD4⁺ T-cell recovery and immune recovery status after initiating ART could be useful regarding T-cell reservoirs investigations in HIV subjects.

SUBMITTER: Ceausu A

PROVIDER: S-EPMC6823538 | biostudies-literature |

REPOSITORIES: biostudies-literature

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TSLP and IL-7R Variants Are Associated with Persistent Atopic Dermatitis.

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Gene variation in IL-7 receptor (IL-7R)α affects IL-7R response in CD4+ T cells in HIV-infected individuals.

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IL-15 sustains IL-7R independent ILC2 and ILC3 development

Project description:ILC3 contain 3 well-defined subsets, CCR6+ ILC3, NKp46+ ILC3, and CCR6–NKp46– DN ILC3. These subsets had not previously been transcriptionally compared and the extent to which they had shared or unique transcriptional profiles remained unclear. We used microarray to determine transcriptional differences between these 3 subsets and to find putative factors that support the survival of CCR6+ ILC3 during cytokine depletion.

2017-02-10 | GSE92693 | GEO

IL-7R α polymorphisms in 60 Iranian multiple sclerosis patients.

Project description:BackgroundMultiple sclerosis (MS), a chronic inflammatory demyelinating disorder with neurodegenerative aspects, is more common among young adults, particularly women.MethodsThis molecular study was designed to investigate the IL-7R α chain gene in Iranian MS patients. We studied 60 MS patients, diagnosed based on 2005 R-McDonald criteria and 60 apparently healthy individuals as the control group. DNA was extracted from whole blood cells using MBST/IRAN Extraction kit and all samples were screened for possible sequence variation in three regions including promoter, exon 2 and exon 4 with single strand conformation polymorphism (SSCP).ResultsThe alterations were confirmed with direct sequencing by ABI 3730XL. Although no mutation was detected in the studied regions, eight single nucleotide polymorphisms (SNPs) consisting of rs71617734 in promoter; rs35967524, rs11567704, rs1494558, rs11567705 and rs969128 in exon 2 as well as rs1494555 and rs2228141 in exon 4 were observed. The rs1494558 in exon 2 and rs1494555 in exon 4 were missense variations. Our results also showed the substitution of isoleucine with threonine in rs1494558 (P.I66T) with this accession number, FR863587 submitted in EMBL bank. The study of exon4 areas revealed two SNPs and two sequence variations, where [p.V138I] Valine substituted with isoleucine (FR863588), as well as a silent nucleotide substitution [P. H165H] in the absence of amino acid alteration. The analysis of the SNP genotype in the controls and the patients, using χ(2) showed no significant association with multiple sclerosis in this group.ConclusionOur study demonstrated the effects of some SNPs on the IL-7R α protein in MS. Further studies are required to reveal the effects of these SNPs on the IL-7R α protein in multiple sclerosis.

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