eISSN: 1644-4124
ISSN: 1426-3912
Central European Journal of Immunology
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vol. 39

Experimental immunology
Modulating effects of leflunomide on the balance of Th17/Treg cells in collagen-induced arthritis DBA/1 mice

Ming Zhu
Qi Xu
Xue-Liang Li
Qiang He
Wei-feng Wang

(Centr Eur J Immunol 2014; 39 (2): 152–158)
Online publish date: 2014/06/27
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To evaluated the effect and mechanism of leflunomide (LEF) in murine model of collage-induced arthritis (CIA) on modulating the balance of Th17/Treg cells. DBA mice were divided into: control, CIA, CIA + LEF and CIA + Ibuprofen group. After 14 days immunization with bovine type II collagen (CII), except control group, mice were orally administered saline (CIA group), LEF or ibuprofen daily for 14 days. The severity of arthritis joint was assessed by using arthritis score. The numbers of CD3 + CD4 + interleukin 17 (IL-17) + Th17 cells and CD4+CD25+Foxp3+ Tregs were determined by flow cytometry, the expression of ROR-γt, Foxp3 and IL-21 mRNA in spleen were quantified by RT-PCR and IL-17, IL-21 and transforming growth factor β (TGF-β) level in serum was measured by ELISA.

In comparison with CIA group, CIA + LEF and CIA + Ibuprofen group reduced the disease severity ob-viously (p < 0.05). Leflunomide reduced Th17 cells, the expression of ROR-γt and IL-21 mRNA (p < 0.05) and the levels of IL-17 and IL-21 in serum. In addition, Ibuprofen but not LEF has effect on Treg cells number, Foxp3 mRNA expression and TGF-β secretion.

These results indicate that LEF effect on the balance od Th17/Treg through suppressing Th17 cells, but not stimulating Treg cells. Leflunomide may act as a potential immunomodulator for the treatment of rheumatoid arthritis (RA).

rheumatoid arthritis, Th17, Leflunomide, Treg cells, ROR-γt, IL-17

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