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Updated: Jun 12, 2026

Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes
Published on: September 26, 2013
Role of IL-17 in the Th1 systemic defects in rheumatoid arthritis through selective IL-12Rbeta2 inhibition
Myew-Ling Toh1, Masanori Kawashima, Arnaud Hot
1Department of Immunology and Rheumatology, Immunogenomics and Inflammation Research Unit EA 4130, University of Lyon, Edouard Herriot Hospital, Lyon, France.
Background:
Patients with rheumatoid arthritis (RA) have a systemic Th1 defect associated with inflammation.
Objective:
To examine the hypothesis that interleukin 17 (IL-17) contributes to this defect.
Methods:
IL-17 effects on Th1 markers were examined on T-bet and interferon gamma (IFNgamma) expression in peripheral blood mononuclear cells (PBMCs) from patients with RA or healthy controls (HC). Receptor specificities were determined by analysis of the Th1-specific IL-12 receptor beta2 (IL-12Rbeta2), Th17-specific IL-23R and the common IL-12Rbeta1 chain expression. Effects of IL-17 or IFNgamma on IL-6, IL-1, IL-8, matrix metalloproteinase-8 (MMP-8) were measured by real-time RT-PCR in RA synovial cells.
Results:
RA PBMCs were less responsive to IL-12-induced IFNgamma than HC PBMCs. IL-12 hyporesponsiveness was increased by IL-17 treatment associated with a selective reduction in IL-12Rbeta2, but not IL-23R, IL-12Rbeta1 or T-bet, which was reversed with IL-17R inhibition. IL-17 inhibited IL-12Rbeta2 expression in developing Th1 cells. In RA synovial cells, IL-17 induced IL-6, IL-1, IL-8 and MMP-8, whereas IFNgamma had minimal or inhibitory effects.
Conclusion:
In RA, IL-12 hyporesponsiveness is associated with IL-17R-mediated downregulation of IL-12Rbeta2 expression. IL-17 may reinforce Th17 lineage commitment and proinflammatory and destructive effects through Th1 inhibition and positive feedback effects in RA synovial cells. Anti-inflammatory effects of IL-17/IL-17R antagonism may include the restoration of protective Th1 responses.
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