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Transcriptomics analysis of allergen-induced inflammatory gene expression in the Four-Core Genotype mouse model.

Carolyn Damilola Ekpruke1, Rachel Alford1, Dustin Rousselle1

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Sex hormones and chromosomes significantly influence allergic inflammation responses to house dust mite (HDM) exposure. Female hormones predominantly affect inflammatory gene expression, highlighting sex-specific pathways in allergic airway inflammation.

Keywords:
Four-Core Genotypesallergic inflammationlung inflammationsex chromosomessex hormones

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Area of Science:

  • Immunology
  • Genetics
  • Respiratory Medicine

Background:

  • Sex differences in allergic inflammation are documented, yet underlying mechanisms remain unclear.
  • Previous studies suggest roles for sex hormones and genes in these disparities.
  • Understanding these differences is crucial for targeted allergic airway inflammation therapies.

Purpose of the Study:

  • To investigate sex-specific inflammatory responses to house dust mite (HDM) challenge.
  • To identify differentially expressed genes (DEGs) and regulatory pathways in lung tissue using the Four-Core Genotype (FCG) mouse model.
  • To elucidate the contributions of sex hormones and chromosomes to allergic airway inflammation.

Main Methods:

  • Utilized the Four-Core Genotype (FCG) mouse model (XXM, XXF, XYM, XYF) for HDM challenge.
  • Analyzed eosinophils and neutrophils in bronchoalveolar lavage (BAL) fluid.
  • Performed gene expression profiling using Templated Oligo-Sequencing (TempO-Seq) and differential gene expression analysis (DESeq2).
  • Conducted gene enrichment analysis using Ingenuity Pathway Analysis.

Main Results:

  • Identified 2,863 differentially expressed genes (DEGs) in response to HDM.
  • Observed increased eosinophilia and neutrophilia in HDM-treated mice, most pronounced in the XYF phenotype.
  • Demonstrated a predominant effect of female hormones over chromosomes on inflammatory responses.
  • Found that female chromosomes led to more downregulated genes in HDM-exposed mice, with an opposite effect in controls.
  • Noted overrepresentation of inflammatory response genes in XXM and XYF genotypes upon HDM challenge.

Conclusions:

  • Sex hormones and chromosomes play significant roles in inflammatory responses to HDM.
  • Female hormones exert a predominant influence on allergic airway inflammation, mediated by inflammatory DEGs.
  • Findings reveal sex-specific gene expression patterns and pathways, advancing understanding of sex disparities in allergic airway inflammation.
  • Gene expression profiling provides critical insights into disease mechanisms and therapeutic responses.