Background Systemic sclerosis (SSc) is an autoimmune disease that has three major components: inflammation, fibrosis, and vasculopathy. T-helper 17 cell (Th17) and regulatory T cell (Treg) are considered to be ...Background Systemic sclerosis (SSc) is an autoimmune disease that has three major components: inflammation, fibrosis, and vasculopathy. T-helper 17 cell (Th17) and regulatory T cell (Treg) are considered to be critical for autoimmune disease pathogenesis. The role of Th17 and Treg in SSc is still unclear. The aim of this study was to detect the presence of Th17s and CD4*CD25~ Tregs in peripheral blood samples from SSc patients and to investigate the possible roles of these two T cell subsets in SSc pathogenesis. Methods Th17s (CD4 and IL-17 positive) and CD4*CD25~ Tregs (CD4, CD25 and Foxp3 positive) in the peripheral blood mononuclear cells of 53 SSc patients and 27 healthy controls were counted by flow cytometry. The differences between SSc and control patients were analyzed. Clinical parameters, including disease duration, duration of the second symptoms, Modified Rodnan Skin Score (MRSS), anti-topoisomerase I antibody, anti-U1 ribonucleoprotein (RNP) antibody, systemic involvements, pulmonary function test (PFT) and high resolution computed tomography (HRCT) score were prospectively collected following EUSTAR (EULAR scleroderma trial and research group) protocols. The correlations between the experimental and clinical data were investigated. Results The ratio of Th17 in SSc patients was significantly elevated compared to healthy controls (8.74% vs. 4.41%, P 〈0.001). The amount of Th17 was positively correlated with disease duration (R=-0.531, P=-0.013) and duration of the second symptoms (R=-0.505, P=0.023). The ratio of CD4*CD25* Treg in SSc patients also significantly differed from the healthy controls (3.04% vs. 2.24%, P=0.018). Elevated Tregs were more frequently observed in patients with a high interstitial lung disease (ILD) score on computed tomography (24/36) compared with patients with normal ILD scores (4/12, ,P=-0.043). Elevated Tregs were also more often observed in patients with low carbon monoxide diffusing capacity (DLCO) (24/34) compared with patients with normal DLCO (4/11, P=0.042). Conclusions T cell abnormalities are remarkable in systemic sclerosis. Th17s proliferate and their numbers increase with lengthened disease duration. Th17s might participate in both inflammation and fibrosis by secreting IL-17. CD4+CD25+ Tress also proliferate in SSc and may play important roles in promoting fibrosis.展开更多
目的检测哮喘小鼠与对照小鼠肺组织中Th1、Th2、Th17及Foxp3+Treg细胞占CD4+T细胞百分比,探讨哮喘小鼠中Foxp3+Treg/Th17比值变化及其在哮喘中的意义。方法将6周清洁级Balb/c小鼠随机分为对照组(control)和哮喘组(OVA),哮喘组给予OVA致...目的检测哮喘小鼠与对照小鼠肺组织中Th1、Th2、Th17及Foxp3+Treg细胞占CD4+T细胞百分比,探讨哮喘小鼠中Foxp3+Treg/Th17比值变化及其在哮喘中的意义。方法将6周清洁级Balb/c小鼠随机分为对照组(control)和哮喘组(OVA),哮喘组给予OVA致敏和激发,建立哮喘小鼠模型,对照组用PBS代替OVA。最后1次激发后24 h内检测支气管肺泡灌洗液(BALF)中细胞总数及细胞分类计数;HE染色制作肺组织病理切片,光镜下观察病理变化;小鼠肺功能仪检测小鼠气道高反应性;流式细胞术检测小鼠肺组织中Th1、Th2、Th17、Foxp3+Treg细胞占CD4+T细胞百分比。结果哮喘组BALF细胞总数、淋巴细胞、嗜酸性粒细胞及中性粒细胞比例显著高于对照组,肺部炎症反应与气道高反应显著高于对照组。哮喘组小鼠肺组织中Th2、Th17细胞百分比明显高于对照组[分别为(0.83±0.08)%vs(0.50±0.03)%;(1.74±0.17)%vs(1.07±0.07)%,P<0.01];而Th1、Foxp3+Treg细胞百分比显著低于对照组[分别为(1.39±0.14)%vs(2.56±0.18)%;(4.87±0.35)%vs(7.67±0.44)%,P<0.001];哮喘组Th1/Th2及Foxp3+Treg/Th17明显低于对照组(分别为1.66±0.17 vs 5.19±0.56;3.02±0.49 vs 7.38±0.71,P<0.001)。结论除Th1/Th2失衡外,Foxp3+Treg/Th17失衡在哮喘发病中亦有重要作用。展开更多
文摘Background Systemic sclerosis (SSc) is an autoimmune disease that has three major components: inflammation, fibrosis, and vasculopathy. T-helper 17 cell (Th17) and regulatory T cell (Treg) are considered to be critical for autoimmune disease pathogenesis. The role of Th17 and Treg in SSc is still unclear. The aim of this study was to detect the presence of Th17s and CD4*CD25~ Tregs in peripheral blood samples from SSc patients and to investigate the possible roles of these two T cell subsets in SSc pathogenesis. Methods Th17s (CD4 and IL-17 positive) and CD4*CD25~ Tregs (CD4, CD25 and Foxp3 positive) in the peripheral blood mononuclear cells of 53 SSc patients and 27 healthy controls were counted by flow cytometry. The differences between SSc and control patients were analyzed. Clinical parameters, including disease duration, duration of the second symptoms, Modified Rodnan Skin Score (MRSS), anti-topoisomerase I antibody, anti-U1 ribonucleoprotein (RNP) antibody, systemic involvements, pulmonary function test (PFT) and high resolution computed tomography (HRCT) score were prospectively collected following EUSTAR (EULAR scleroderma trial and research group) protocols. The correlations between the experimental and clinical data were investigated. Results The ratio of Th17 in SSc patients was significantly elevated compared to healthy controls (8.74% vs. 4.41%, P 〈0.001). The amount of Th17 was positively correlated with disease duration (R=-0.531, P=-0.013) and duration of the second symptoms (R=-0.505, P=0.023). The ratio of CD4*CD25* Treg in SSc patients also significantly differed from the healthy controls (3.04% vs. 2.24%, P=0.018). Elevated Tregs were more frequently observed in patients with a high interstitial lung disease (ILD) score on computed tomography (24/36) compared with patients with normal ILD scores (4/12, ,P=-0.043). Elevated Tregs were also more often observed in patients with low carbon monoxide diffusing capacity (DLCO) (24/34) compared with patients with normal DLCO (4/11, P=0.042). Conclusions T cell abnormalities are remarkable in systemic sclerosis. Th17s proliferate and their numbers increase with lengthened disease duration. Th17s might participate in both inflammation and fibrosis by secreting IL-17. CD4+CD25+ Tress also proliferate in SSc and may play important roles in promoting fibrosis.
文摘目的检测哮喘小鼠与对照小鼠肺组织中Th1、Th2、Th17及Foxp3+Treg细胞占CD4+T细胞百分比,探讨哮喘小鼠中Foxp3+Treg/Th17比值变化及其在哮喘中的意义。方法将6周清洁级Balb/c小鼠随机分为对照组(control)和哮喘组(OVA),哮喘组给予OVA致敏和激发,建立哮喘小鼠模型,对照组用PBS代替OVA。最后1次激发后24 h内检测支气管肺泡灌洗液(BALF)中细胞总数及细胞分类计数;HE染色制作肺组织病理切片,光镜下观察病理变化;小鼠肺功能仪检测小鼠气道高反应性;流式细胞术检测小鼠肺组织中Th1、Th2、Th17、Foxp3+Treg细胞占CD4+T细胞百分比。结果哮喘组BALF细胞总数、淋巴细胞、嗜酸性粒细胞及中性粒细胞比例显著高于对照组,肺部炎症反应与气道高反应显著高于对照组。哮喘组小鼠肺组织中Th2、Th17细胞百分比明显高于对照组[分别为(0.83±0.08)%vs(0.50±0.03)%;(1.74±0.17)%vs(1.07±0.07)%,P<0.01];而Th1、Foxp3+Treg细胞百分比显著低于对照组[分别为(1.39±0.14)%vs(2.56±0.18)%;(4.87±0.35)%vs(7.67±0.44)%,P<0.001];哮喘组Th1/Th2及Foxp3+Treg/Th17明显低于对照组(分别为1.66±0.17 vs 5.19±0.56;3.02±0.49 vs 7.38±0.71,P<0.001)。结论除Th1/Th2失衡外,Foxp3+Treg/Th17失衡在哮喘发病中亦有重要作用。