title: IL-22-producing CD4+T cells in the treatment response of rheumatoid arthritis to combination therapy with methotrexate and leflunomide.
abstract: 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.
authors.affiliation: The First Hospital of Jilin University, Department of Rheumatology, Changchun, 130021, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhong
authors.affiliation: The First Hospital of Jilin University, Department of Rheumatology, Changchun, 130021, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhao
authors.affiliation: The First Hospital of Jilin University, Department of Rheumatology, Changchun, 130021, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: The First Hospital of Jilin University, Department of Rheumatology, Changchun, 130021, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007378:Interleukins / Q000097:blood / Q000276:immunology*; D007555:Isoxazoles / Q000627:therapeutic use*; D000077339:Leflunomide; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D016896:Treatment Outcome; D000097043:Interleukin-22
chemical_list: D018501:Antirheumatic Agents; D007378:Interleukins; D007555:Isoxazoles; D000077339:Leflunomide; D008727:Methotrexate; D000097043:Interleukin-22