Recent studies have demonstrated a central role for plasma cells in the development of autoimmune diseases,such as systemic lupus erythematosus(SLE).Currently,both the phenotypic features and functional regulation of ...Recent studies have demonstrated a central role for plasma cells in the development of autoimmune diseases,such as systemic lupus erythematosus(SLE).Currently,both the phenotypic features and functional regulation of autoreactive plasma cells during SLE pathogenesis remain largely unclear.In this study,we first found that a major subset of IL-17 receptor-expressing plasma cells potently produced anti-dsDNA IgG upon IL-17A(IL-17)stimulation in SLE patients and lupus mice.Using a humanized lupus mouse model,we showed that the transfer of Th17 cell-depleted PBMCs from lupus patients resulted in a significantly reduced plasma cell response and attenuated renal damage in recipient mice compared to the transfer of total SLE PBMCs.Moreover,long-term BrdU incorporation in lupus mice detected highly enriched long-lived BrdU+subsets among IL-17 receptor-expressing plasma cells.Lupus mice deficient in IL-17 or IL-17 receptor C(IL-17RC)exhibited a diminished plasma cell response and reduced autoantibody production with attenuated renal damage,while the adoptive transfer of Th17 cells triggered the plasma cell response and renal damage in IL-17-deficient lupus mice.In reconstituted chimeric mice,IL-17RC deficiency resulted in severely impaired plasma cell generation but showed no obvious effect on germinal center B cells.Further mechanistic studies revealed that IL-17 significantly promoted plasma cell survival via p38-mediated Bcl-xL transcript stabilization.Together,our findings identified a novel function of IL-17 in enhancing plasma cell survival for autoantibody production in lupus pathogenesis,which may provide new therapeutic strategies for the treatment of SLE.展开更多
Objective: This study was carried out to test the effects of methotrexate (MTX) and black seed oil (BSO) on pristane-induced arthritis (PIA) in rats.Methods: Inbred dark agouti (DA) rats were induced by a single subcu...Objective: This study was carried out to test the effects of methotrexate (MTX) and black seed oil (BSO) on pristane-induced arthritis (PIA) in rats.Methods: Inbred dark agouti (DA) rats were induced by a single subcutaneous injection of pristane,and then treated with MTX or BSO.Arthritis severity was evaluated macroscopically and microscopically.Plasma nitric oxide (NO) concentration was determined by the Griess method and cytokine mRNA expression in the spleen was detected by the real-time reverse transcription-polymerase chain reaction (RT-PCR).Results: The clinical arthritis severity was decreased after MTX treatment,while the BSO groups did not show significant changes compared with the disease group.The plasma NO level of the MTX group was significantly decreased compared with the disease group,but the BSO groups showed no difference from the disease group in plasma NO levels.The interferon-γ (IFN-γ) and interleukin-17A (IL-17A) mRNA expressions in the spleens were significantly decreased in the MTX group,but only showed a declining trend in the BSO groups compared with the disease group.Neither MTX nor BSO had an effect on the mRNA expressions of IL-4,transforming growth factor β (TGF-β),and tumor necrosis factor-α (TNF-α) in the spleen.Conclusions: MTX,but not BSO,can reduce the arthritis severity and decrease the mRNA expressions of IFN-γ and IL-17A in pristane-induced arthritis of rats.展开更多
目的:观察参地颗粒对慢性肾炎脾肾亏虚型患者Th17细胞免疫功能的干预作用。方法:90例慢性肾炎患者按随机数字表法分为试验组和对照组各45例,2组均给予西医基础治疗,对照组加用缬沙坦胶囊(代文)80 mg/d,试验组在对照组基础上加用参地颗...目的:观察参地颗粒对慢性肾炎脾肾亏虚型患者Th17细胞免疫功能的干预作用。方法:90例慢性肾炎患者按随机数字表法分为试验组和对照组各45例,2组均给予西医基础治疗,对照组加用缬沙坦胶囊(代文)80 mg/d,试验组在对照组基础上加用参地颗粒,2组疗程均为12周。观察24 h尿蛋白定量(24 h Upro)、尿红细胞计数(URBC),并采用流式细胞技术检测外周血CD4^+、CD8^+和Th17细胞含量,酶联免疫吸附法检测血清白介素-17(IL-17)水平。结果:试验组疾病疗效总有效率显著高于对照组。试验组治疗后24 h Upro、URBC与治疗前比较均显著降低,且24 h Upro亦显著低于同期治疗后的对照组。试验组治疗后的Th17含量及IL-17水平与治疗前比较均有显著降低,CD4^+、CD4^+/CD8^+比值显著提升,且其CD4^+/CD8^+比值、Th17含量及IL-17水平变化与对照组比较亦差异有统计学意义。结论:参地颗粒可以通过调节Th17细胞功能,从而改善慢性肾炎脾肾亏虚型患者的免疫功能,发挥临床疗效。展开更多
目的：观察肺抑瘤合剂联合AP（培美曲塞＋顺铂）化疗方案治疗非小细胞肺癌临床疗效及对细胞炎性因子的影响。方法：选择符合纳入标准的非小细胞肺癌患者62例,采用简单数字的随机方法分为对照组和治疗组,每组31例。两组均采用规范的西药...目的：观察肺抑瘤合剂联合AP（培美曲塞＋顺铂）化疗方案治疗非小细胞肺癌临床疗效及对细胞炎性因子的影响。方法：选择符合纳入标准的非小细胞肺癌患者62例,采用简单数字的随机方法分为对照组和治疗组,每组31例。两组均采用规范的西药治疗,对照组给予AP（培美曲塞＋顺铂）化疗方案,在此基础上给予复方斑蝥胶囊口服,3粒/次,2次/d。治疗组在AP（培美曲塞＋顺铂）方案基础上给予肺抑瘤合剂口服,每次100 m L,3次/d。观察两组患者治疗前后生活质量评分、临床证候积分、血清中细胞炎性因子白细胞介素（IL）-6,IL^（-1）7,前列腺素E2（PGE2）水平变化,以及治疗后两组间瘤体改善情况、不良事件发生率,统计临床疗效。结果：治疗组治疗后在生活质量评分、证候积分（咳嗽、咳血、胸痛、乏力、发热）、血清中细胞炎性因子（IL-6,IL^（-1）7,PGE2）水平较治疗前明显改善,且优于对照组（P〈0.05）;治疗组治疗后瘤体的稳定率明显优于对照组（P〈0.05）,且不良事件发生率低于对照组（P〈0.05）。结论：肺抑瘤合剂联合AP化疗方案能更有效地改善非小细胞肺癌患者生活质量、临床症状及实体瘤大小,降低细胞炎性因子在患者血清中的表达,降低临床不良事件的发生,值得进一步推广研究。展开更多
基金funded by grants from the National Natural Science Foundation of China(Nos.81771761,91842304,and 81901635)Chongqing International Institute for Immunology(2020YJC10)Sanming Project of Medicine in Shenzhen(SZSM201512019)。
文摘Recent studies have demonstrated a central role for plasma cells in the development of autoimmune diseases,such as systemic lupus erythematosus(SLE).Currently,both the phenotypic features and functional regulation of autoreactive plasma cells during SLE pathogenesis remain largely unclear.In this study,we first found that a major subset of IL-17 receptor-expressing plasma cells potently produced anti-dsDNA IgG upon IL-17A(IL-17)stimulation in SLE patients and lupus mice.Using a humanized lupus mouse model,we showed that the transfer of Th17 cell-depleted PBMCs from lupus patients resulted in a significantly reduced plasma cell response and attenuated renal damage in recipient mice compared to the transfer of total SLE PBMCs.Moreover,long-term BrdU incorporation in lupus mice detected highly enriched long-lived BrdU+subsets among IL-17 receptor-expressing plasma cells.Lupus mice deficient in IL-17 or IL-17 receptor C(IL-17RC)exhibited a diminished plasma cell response and reduced autoantibody production with attenuated renal damage,while the adoptive transfer of Th17 cells triggered the plasma cell response and renal damage in IL-17-deficient lupus mice.In reconstituted chimeric mice,IL-17RC deficiency resulted in severely impaired plasma cell generation but showed no obvious effect on germinal center B cells.Further mechanistic studies revealed that IL-17 significantly promoted plasma cell survival via p38-mediated Bcl-xL transcript stabilization.Together,our findings identified a novel function of IL-17 in enhancing plasma cell survival for autoantibody production in lupus pathogenesis,which may provide new therapeutic strategies for the treatment of SLE.
基金Project supported by the National Natural Science Foundation of China (Nos.30630058,30801027,and 30571725)the Shaanxi Province International Cooperation Foundation of China (No.2007-KW-06)
文摘Objective: This study was carried out to test the effects of methotrexate (MTX) and black seed oil (BSO) on pristane-induced arthritis (PIA) in rats.Methods: Inbred dark agouti (DA) rats were induced by a single subcutaneous injection of pristane,and then treated with MTX or BSO.Arthritis severity was evaluated macroscopically and microscopically.Plasma nitric oxide (NO) concentration was determined by the Griess method and cytokine mRNA expression in the spleen was detected by the real-time reverse transcription-polymerase chain reaction (RT-PCR).Results: The clinical arthritis severity was decreased after MTX treatment,while the BSO groups did not show significant changes compared with the disease group.The plasma NO level of the MTX group was significantly decreased compared with the disease group,but the BSO groups showed no difference from the disease group in plasma NO levels.The interferon-γ (IFN-γ) and interleukin-17A (IL-17A) mRNA expressions in the spleens were significantly decreased in the MTX group,but only showed a declining trend in the BSO groups compared with the disease group.Neither MTX nor BSO had an effect on the mRNA expressions of IL-4,transforming growth factor β (TGF-β),and tumor necrosis factor-α (TNF-α) in the spleen.Conclusions: MTX,but not BSO,can reduce the arthritis severity and decrease the mRNA expressions of IFN-γ and IL-17A in pristane-induced arthritis of rats.
文摘目的:观察参地颗粒对慢性肾炎脾肾亏虚型患者Th17细胞免疫功能的干预作用。方法:90例慢性肾炎患者按随机数字表法分为试验组和对照组各45例,2组均给予西医基础治疗,对照组加用缬沙坦胶囊(代文)80 mg/d,试验组在对照组基础上加用参地颗粒,2组疗程均为12周。观察24 h尿蛋白定量(24 h Upro)、尿红细胞计数(URBC),并采用流式细胞技术检测外周血CD4^+、CD8^+和Th17细胞含量,酶联免疫吸附法检测血清白介素-17(IL-17)水平。结果:试验组疾病疗效总有效率显著高于对照组。试验组治疗后24 h Upro、URBC与治疗前比较均显著降低,且24 h Upro亦显著低于同期治疗后的对照组。试验组治疗后的Th17含量及IL-17水平与治疗前比较均有显著降低,CD4^+、CD4^+/CD8^+比值显著提升,且其CD4^+/CD8^+比值、Th17含量及IL-17水平变化与对照组比较亦差异有统计学意义。结论:参地颗粒可以通过调节Th17细胞功能,从而改善慢性肾炎脾肾亏虚型患者的免疫功能,发挥临床疗效。
文摘目的：观察肺抑瘤合剂联合AP（培美曲塞＋顺铂）化疗方案治疗非小细胞肺癌临床疗效及对细胞炎性因子的影响。方法：选择符合纳入标准的非小细胞肺癌患者62例,采用简单数字的随机方法分为对照组和治疗组,每组31例。两组均采用规范的西药治疗,对照组给予AP（培美曲塞＋顺铂）化疗方案,在此基础上给予复方斑蝥胶囊口服,3粒/次,2次/d。治疗组在AP（培美曲塞＋顺铂）方案基础上给予肺抑瘤合剂口服,每次100 m L,3次/d。观察两组患者治疗前后生活质量评分、临床证候积分、血清中细胞炎性因子白细胞介素（IL）-6,IL^（-1）7,前列腺素E2（PGE2）水平变化,以及治疗后两组间瘤体改善情况、不良事件发生率,统计临床疗效。结果：治疗组治疗后在生活质量评分、证候积分（咳嗽、咳血、胸痛、乏力、发热）、血清中细胞炎性因子（IL-6,IL^（-1）7,PGE2）水平较治疗前明显改善,且优于对照组（P〈0.05）;治疗组治疗后瘤体的稳定率明显优于对照组（P〈0.05）,且不良事件发生率低于对照组（P〈0.05）。结论：肺抑瘤合剂联合AP化疗方案能更有效地改善非小细胞肺癌患者生活质量、临床症状及实体瘤大小,降低细胞炎性因子在患者血清中的表达,降低临床不良事件的发生,值得进一步推广研究。
