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Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes
Published on: September 26, 2013
IL-23R rs11209026 polymorphism modulates IL-17A expression in patients with rheumatoid arthritis
J Hazlett1, L K Stamp, T Merriman
1Leukocyte Inflammation Research Laboratory, Department of Physiology, University of Otago, Dunedin, New Zealand.
Genes and Immunity
|December 2, 2011
Summary
Genetic variations in the interleukin-23 receptor (IL-23R) gene may influence interleukin-17A (IL-17A) levels in rheumatoid arthritis (RA) patients. Specifically, the IL-23R rs11209026 polymorphism is linked to altered IL-17A serum concentrations.
Area of Science:
- Immunology
- Genetics
- Rheumatology
Background:
- The interleukin-17/interleukin-23 (IL-17/IL-23) signaling pathway plays a critical role in the inflammatory processes underlying rheumatoid arthritis (RA).
- IL-23 promotes the survival of T-helper 17 (Th17) cells, which are key producers of IL-17A, a pro-inflammatory cytokine implicated in RA pathogenesis.
- Conversely, IL-12 counteracts IL-17A production by driving Th1-cell differentiation.
Purpose of the Study:
- To investigate the association between polymorphisms in the IL-23R, IL-12, and IL-21 genes and serum cytokine concentrations in patients with rheumatoid arthritis.
- To determine if specific genetic variants influence the levels of key cytokines involved in the IL-17/IL-23 axis in RA.
Main Methods:
- Serum cytokine levels were quantified in 81 RA patients using bead-based multiplex assays.
- Genotyping was performed for polymorphisms in the IL-23R (rs11209026), IL-12B (rs3213337, rs17860508), and IL-21 (rs6822844) genes.
- Statistical analyses were conducted to compare cytokine concentrations between different genotype groups.
Main Results:
- A significant association was observed between the IL-23R rs11209026 polymorphism and serum IL-17A levels. Patients homozygous for the major allele exhibited significantly higher IL-17A concentrations compared to those with the minor allele (P = 0.017).
- No significant differences in serum cytokine concentrations were found concerning polymorphisms in the IL-12B or IL-21 genes.
- Detectable levels of targeted cytokines, including IL-17A, were found in a substantial proportion of the patient cohort.
Conclusions:
- The Arg381Gln substitution in the IL-23 receptor (IL-23R) may influence serum IL-17A concentrations in rheumatoid arthritis patients.
- Individuals with the 381Gln allele might require higher IL-23 concentrations to achieve similar IL-17A levels as those with the 381Arg allele, suggesting altered IL-23R function.
- These findings highlight the potential role of IL-23R genetic variations in RA pathogenesis and warrant further functional investigation.
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