文章基本信息

标题：IL-22-producing CD4+T cells in the treatment response of rheumatoid arthritis to combination therapy with methotrexate and leflunomide
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作者：Wei Zhong ; Ling Zhao ; Tao Liu 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2017
卷号：7
期号：1
DOI：10.1038/srep41143
语种：English
出版社：Springer Nature
摘要：T cells are key players in immune-mediated rheumatoid arthritis (RA). We previously reported that interleukin (IL)-22(+)CD4(+)T helper (IL-22(+) Th) cells and IL-22 critically control the pathogenesis of RA. Here we monitored circulating levels of different IL-22(+) Th cell subsets and measured plasma levels of IL-22, IL-17, and interferon (IFN)-γ in 60 patients with active RA following 12-week combination methotrexate (MTX) and leflunomide (LEF) therapy (MTX+LEF) and 20 healthy individuals. We found the frequencies of circulating IFN-γ(-)IL-17(-)IL-22(+) (Th22), IFN-γ(-)IL-17(+) (total Th17), IFN-γ(+)IL-17(-)IL-22(+) (IL-22(+)Th1) cells, and IFN-γ(-)IL-17(+)IL-22(+) (IL-22(+)Th17) cells, as well as the plasma levels of IL-22, IL-17 and IFN-γ to be significantly reduced in RA patients that responded to treatment, but not in non-responders. Reductions in plasma IL-22 level significantly correlated with percentage of circulating Th22 cells and the decrease of plasma IL-22 level correlated with the reduction of DAS28 in responders. Our data suggests that circulating Th22 cells and plasma IL-22 level play a detrimental role in RA. The combination MTX+LEF therapy, by targeting Th22 cells and reducing IL-22 level, relieves the immune defects and ameliorates symptoms of RA. This study provides novel mechanistic understanding of the pathogenesis of RA, which may promote a design of better therapies for RA.