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首页> 外文期刊>Clinical and Experimental Immunology: An Official Journal of the British Society for Immunology >Recombinant Salmonella typhimurium outer membrane protein A is recognized by synovial fluid CD8 cells and stimulates synovial fluid mononuclear cells to produce interleukin (IL)-17/IL-23 in patients with reactive arthritis and undifferentiated spondyloarthropathy
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Recombinant Salmonella typhimurium outer membrane protein A is recognized by synovial fluid CD8 cells and stimulates synovial fluid mononuclear cells to produce interleukin (IL)-17/IL-23 in patients with reactive arthritis and undifferentiated spondyloarthropathy

机译：重组鼠伤寒沙门氏菌外膜蛋白A被滑液CD8细胞识别并刺激滑液单核细胞产生反应性关节炎和未分化的脊椎骨关节炎的白介素（IL）-17 / IL-23

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摘要

In developing countries, one-third of patients with reactive arthritis (ReA) and undifferentiated spondyloarthropathy (uSpA) are triggered by Salmonella typhimurium. Synovial fluid mononuclear cells (SFMCs) of patients with ReA and uSpA proliferate to low molecular weight fractions (lmwf) of outer membrane proteins (Omp) of S. typhimurium. To characterize further the immunity of Omp of Salmonella, cellular immune response to two recombinant proteins of lmwf, OmpA and OmpD of S. typhimurium (rOmpA/D-sal) was assessed in 30 patients with ReA/uSpA. Using flow cytometry, 17 of 30 patients' SF CD8(+) T cells showed significant intracellular interferon (IFN)- to Omp crude lysate of S. typhimurium. Of these 17, 11 showed significantly more CD8(+)CD69(+) IFN- T cells to rOmpA-sal, whereas only four showed reactivity to rOmpD-sal. The mean stimulation index was significantly greater in rOmpA-sal than rOmpD-sal [30 (15-65) versus 15 (10-275), P < 0005]. Similarly, using enzyme-linked immunospot (ELISPOT) in these 17 patients, the mean spots of IFN--producing SFMCs were significantly greater in rOmpA-sal than rOmpD-sal [449 (35-1307) versus 1925 (6-41), P < 005]. SFMCs stimulated by rOmpA-sal produced significantly more proinflammatory cytokines than rOmpD-sal: IFN- [144 (039-2042) versus 072 (0048-915) ng/ml, P < 005], interleukin (IL)-17 [2860 (615-51086) versus 1184 (683-25262) pg/ml, P < 005], IL-23 [7019 (15-116116) versus 2825 (> 15-24152) pg/ml, P < 005] and IL-6 [5978 (203-27336) versus 1017 (0004-19019) ng/ml, P < 005]. The rOmpA-sal-specific CD8(+) T cell response correlated with duration of current synovitis (r = 053, P < 005). Thus, OmpA of S. typhimurium is a target of SF CD8(+) T cells and drives SFMC to produce increased cytokines of the IL-17/IL-23 axis which contribute to the pathogenesis of Salmonella-triggered ReA.
机译：在发展中国家，三分之一的反应性关节炎（ReA）和未分化型脊柱关节炎（uSpA）患者是由鼠伤寒沙门氏菌引发的。 ReA和uSpA患者的滑液单核细胞（SFMC）增殖为鼠伤寒沙门氏菌外膜蛋白（Omp）的低分子量级分（lmwf）。为了进一步表征沙门氏菌Omp的免疫性，在30名ReA / uSpA患者中评估了对两种重组蛋白lmwf，鼠伤寒沙门氏菌OmpA和OmpD的细胞免疫应答（rOmpA / D-sal）。使用流式细胞仪，30例患者的SF CD8（+）T细胞中有17例显示鼠伤寒沙门氏菌的细胞内干扰素（IFN）-到Omp粗裂解物。在这17个中，有11个显示出更多的CD8（+）CD69（+）IFN-T细胞对rOmpA-sal，而只有四个显示对rOmpD-sal的反应性。 rOmpA-sal中的平均刺激指数显着大于rOmpD-sal [30（15-65）对15（10-275），P <0005]。同样，在这17名患者中使用酶联免疫斑点（ELISPOT），rOmpA-sal中产生IFN的SFMC的平均斑点显着大于rOmpD-sal [449（35-1307）与1925（6-41）， P <005]。与rOmpD-sal相比，rOmpA-sal刺激的SFMC产生的促炎细胞因子明显更多：IFN- [144（039-2042）与072（0048-915）ng / ml，P <005]，白介素（IL）-17 [2860（ 615-51086）对1184（683-25262）pg / ml，P <005]，IL-23 [7019（15-116116）对2825（> 15-24152）pg / ml，P <005]和IL-6 [5978（203-27336）与1017（0004-19019）ng / ml，P <005]。 rOmpA-sal特异性CD8（+）T细胞反应与当前滑膜炎的持续时间相关（r = 053，P <005）。因此，鼠伤寒沙门氏菌的OmpA是SF CD8（+）T细胞的靶标，并驱动SFMC产生IL-17 / IL-23轴增加的细胞因子，这有助于沙门氏菌触发的ReA的发病机理。

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