title: Natural killer-22 cells in the synovial fluid of patients with rheumatoid arthritis are an innate source of interleukin 22 and tumor necrosis factor-α.
abstract: OBJECTIVE
  To determine the role of natural killer (NK)-22 cells in the pathogenesis of rheumatoid arthritis (RA).
  
  
  METHODS
  Using flow cytometry, the proportions of NK-22 cells and intracellular contents of perforin, granzyme B, and interferon-γ (IFN-γ) were determined in the peripheral blood (PB) and synovial fluid (SF) of patients with RA and healthy individuals. The levels of interleukin 22 (IL-22) and tumor necrosis factor-α (TNF-α) in the NK-22 supernatant and gene expressions were measured using ELISA and QuantiGene Plex assay, respectively. The effect of NK-22 supernatant on the proliferation of fibroblast-like synoviocytes (FLS) and recombinant human IL-22 (rhIL-22) on the production of monocyte chemoattractant protein 1 (MCP-1) by RA FLS was detected using the yellow tetrazolium salt method and ELISA, respectively. The relationship between the proportions of NK-22 cells and disease activity was analyzed.
  
  
  RESULTS
  NKp44 and CCR6 were expressed in a larger population of SF NK cells than in the PB NK cells of patients with RA. NK-22 cells produce low content of perforin, granzyme B, and IFN-γ. NK-22 cells in vitro can secrete IL-22 and TNF-α and there was increased messenger RNA coding for IL-22 and TNF-α. NK-22 supernatant can induce the proliferation of RA FLS. Addition of IL-22 antibody plus TNF-α antibody inhibited the proliferation of FLS induced by the NK-22 supernatant. Both rhIL-22 1 ng/ml and rhIL-22 10 ng/ml induced the production of MCP-1 by RA FLS. The NK-22 proportions were positively correlated with disease activity.
  
  
  CONCLUSIONS
  NK-22 cells are increased in patients with RA and might play a role in the pathogenesis of RA through the production of IL-22 and TNF-α. The proportion of NK-22 cells and disease activity were highly correlated.
authors.affiliation: Department of Rheumatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ren
authors.forename: Zhitao
authors.initials: Z
authors.lastname: Feng
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Lv
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Chen
authors.forename: Juan
authors.initials: J
authors.lastname: Li
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D049109:Cell Proliferation; D018932:Chemokine CCL2 / Q000378:metabolism; D005260:Female; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013582:Synovial Fluid / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D000097043:Interleukin-22
chemical_list: D018932:Chemokine CCL2; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D000097043:Interleukin-22