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IL-17-producing cells in ankylosing spondylitis patients show gender-based differences in gene expression
C.M. Lee1, E.R. Chan2, D. Schueller3, M. Breitman4, M. Haghiac5, M. Magrey6
- University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
- Case Western Reserve University, Cleveland, OH, USA.
- MetroHealth Medical Center, Cleveland, OH, USA.
- Case Western Reserve University, Cleveland, and MetroHealth Medical Center, Cleveland, OH, USA.
- MetroHealth Medical Center, Cleveland, OH, USA.
- University Hospitals Cleveland Medical Center, Cleveland, and Case Western Reserve University, Cleveland, OH, USA. marina.magrey@uhhospitals.org
CER16939
2024 Vol.42, N°5
PI 1057, PF 1066
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PMID: 38436300 [PubMed]
Received: 21/06/2023
Accepted : 20/11/2023
In Press: 03/03/2024
Published: 14/05/2024
Abstract
OBJECTIVES:
Gender has been shown to impact disease expression in ankylosing spondylitis (AS) and Th17 cells play a key role in AS pathogenesis. To better understand what Th17-associated immune pathways are different between men and women, we compared the transcriptome of IL-17-enriched peripheral blood mononuclear cells (PBMCs) in male and female AS patients, with a particular focus on inflammatory cytokine genes.
METHODS:
PBMCs were collected from 10 female and 11 male AS patients at the Clinical Research Unit of MetroHealth Medical Center. IL-17-enriched PBMCs were isolated and stimulated with CytoStim. RNA-sequencing (RNA-seq) was performed on the samples, and the data were analysed using iPathwayGuide. Inflammatory markers and genes related to Th17 differentiation and function were identified based on previous studies.
RESULTS:
RNA-seq identified 12,893 genes with 2,851 genes with p-values <0.05 with distinct patterns of gene expression between male and female AS patients. TGF-β, PGE2, and S100 proteins were significantly upregulated in males. Levels of IL-12B, a Th17 inducer, were lower in males compared to females. Additionally, receptors of IL-6, 12, 23, TGF-β, and PGE2 were downregulated in males, except for IL-17RC, which was upregulated. Genes involved in Th17 differentiation showed differential expression between genders, with elevated expression of BATF, SOCS1, NKD2, and ARID5A in men and decreased expression of FOXO1.
CONCLUSIONS:
Transcriptomic analysis revealed that male AS patients exhibit distinct expression patterns of IL-17 pro-inflammatory genes, which may contribute to the phenotypic differences observed between genders in AS.
