Polymorphisms in the canine IL7R 3′UTR are associated with thymic output in Labrador retriever dogs and influence post-transcriptional regulation by microRNA 185

Angela Holder, Gareth Jones, Francesca Soutter, Donald B. Palmer, Richard Aspinall, Brian Catchpole

Research output: Contribution to journalArticle

Abstract

Interleukin-7 (IL-7) and its receptor (IL-7R) are essential for T cell development in the thymus, and changes in the IL-7/IL-7R pathway have been implicated in age-associated thymic involution which results in a reduction of naïve T cell output. The aim of this study was to investigate the relationship between IL7 and IL7R genetic variation and thymic output in dogs. No single nucleotide polymorphisms (SNPs) were identified in the canine IL7 gene, but a number were present in the canine IL7R gene. Polymorphisms in the IL7R exon 8 and 3′UTR were found to be associated with signal joint T cell receptor excision circle (sj-TREC) values (a biomarker of thymic output) in young and geriatric Labrador retrievers. Additionally, one of the SNPs in the IL7R 3′UTR (SNP 14 c.1371 + 446 A > C) was found to cause a change in the seed-binding site for microRNA 185 which, a luciferase reporter assay demonstrated, caused changes in post-transcriptional regulation, and therefore might be capable of influencing IL-7R expression. The research findings suggest a genetic link between IL7R genotype and thymic output in dogs, which might impact on immune function as these animals age and provide further evidence of the involvement of IL-7/IL-7R pathway in age-associated thymic involution.

Original languageEnglish
Pages (from-to)244-251
Number of pages8
JournalDevelopmental and Comparative Immunology
Volume81
Early online date14 Dec 2017
DOIs
Publication statusPublished - 1 Apr 2018
Externally publishedYes

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Interleukin-7 Receptors
Newfoundland and Labrador
Interleukin-7
MicroRNAs
Canidae
Dogs
Single Nucleotide Polymorphism
T-Lymphocytes
T-Cell Antigen Receptor
Luciferases
Geriatrics
Thymus Gland
Genes
Exons
Seeds
Joints
Biomarkers
Binding Sites
Genotype
Research

Keywords

  • Canine
  • Interleukin-7 receptor
  • Signal joint T cell receptor excision circle
  • Thymic involution

ASJC Scopus subject areas

  • Immunology
  • Developmental Biology

Cite this

Polymorphisms in the canine IL7R 3′UTR are associated with thymic output in Labrador retriever dogs and influence post-transcriptional regulation by microRNA 185. / Holder, Angela; Jones, Gareth; Soutter, Francesca; Palmer, Donald B.; Aspinall, Richard; Catchpole, Brian.

In: Developmental and Comparative Immunology, Vol. 81, 01.04.2018, p. 244-251.

Research output: Contribution to journalArticle

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abstract = "Interleukin-7 (IL-7) and its receptor (IL-7R) are essential for T cell development in the thymus, and changes in the IL-7/IL-7R pathway have been implicated in age-associated thymic involution which results in a reduction of na{\"i}ve T cell output. The aim of this study was to investigate the relationship between IL7 and IL7R genetic variation and thymic output in dogs. No single nucleotide polymorphisms (SNPs) were identified in the canine IL7 gene, but a number were present in the canine IL7R gene. Polymorphisms in the IL7R exon 8 and 3′UTR were found to be associated with signal joint T cell receptor excision circle (sj-TREC) values (a biomarker of thymic output) in young and geriatric Labrador retrievers. Additionally, one of the SNPs in the IL7R 3′UTR (SNP 14 c.1371 + 446 A > C) was found to cause a change in the seed-binding site for microRNA 185 which, a luciferase reporter assay demonstrated, caused changes in post-transcriptional regulation, and therefore might be capable of influencing IL-7R expression. The research findings suggest a genetic link between IL7R genotype and thymic output in dogs, which might impact on immune function as these animals age and provide further evidence of the involvement of IL-7/IL-7R pathway in age-associated thymic involution.",
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