T cell immunoglobulin and mucin domain 3 （Tim-3） is well known to negatively regulate T cells responses, but its role in burn-induced T cells immune suppression remains unclear. In the present study, in order to ide...T cell immunoglobulin and mucin domain 3 （Tim-3） is well known to negatively regulate T cells responses, but its role in burn-induced T cells immune suppression remains unclear. In the present study, in order to identify the relationship between Tim-3 expression and post-burn T cells immune suppression, C57BL/6 mice were subjected to burn injury or sham injury, and the liver and spleen were harvested at the day 1 after operation. The expression level of Tim-3 on hepatic or splenic T cells and the functional properties of Tim-3＋ T cells were evaluated. It was found burn injury induced dramatically elevated Tim-3 expression on both hepatic and splenic CD4＋ and CD8＋ T cells in contrast with the post-burn depletion of T cells. Furthermore, Tim-3 expression was correlated with the suppressive phenotype of T cells following burn injury, including increased expression of anti-inflammatory cytokine IL-10, decreased expression of pro-inflammatory cytokines IFN-γ and TNF-α, reduced T cell proliferation and elevated co-expression of Tim-3 and PD-1. Moreover, Tim-3＋ T cells subsets were more prone to spontaneous apoptosis than Tim-3- T cells subsets. Our findings reinforce the idea that the up-regulated expression of Tim-3 on T cells after burn injury plays an important role in the development and maintenance of burn-induced T cell immune suppression.展开更多
BACKGROUND Irritable bowel syndrome (IBS) is one of the most common functional gastroenterological diseases characterized by abnormal visceral sensitivity and lowgrade inflammation. The role of Clostridium butyricum (...BACKGROUND Irritable bowel syndrome (IBS) is one of the most common functional gastroenterological diseases characterized by abnormal visceral sensitivity and lowgrade inflammation. The role of Clostridium butyricum (C. butyricum) in reducing intestinal low-grade inflammation via immune pathways has been well defined. However, the detailed mechanisms of the effects of C. butyricum on intestinal mucosal immunity, especially on immune cells of the lamina propria, remain unclear. Dendritic cells (DCs), which are important immune cells, secrete proinflammatory cytokines (IL-1β, IL-6, and others) and express T cell immunoglobulin and mucin domain-3 (TIM3), promoting proliferation and activation of DCs, and mediating Th1 and Th17 inflammatory responses. AIM To investigate the role of DCs in the development of IBS in a rat model and to understand the regulation of DCs after C. butyricum intervention. METHODS An IBS animal model was established using C57BL/6 mice, and C. butyricum was continuously administered via the intragastric route to simulate different intestinal immune states. Intestinal visceral hypersensitivity and histopathology were assessed using the abdominal withdrawal reflex (AWR) test and hematoxylin & eosin (H&E) staining, respectively. The expression of proinflammatory cytokines (IL-1β and IL-6) and TIM3 was analyzed by Western blot analysis and real-time PCR. Flow cytometry was applied to analyze the quantity, function, and membrane molecule TIM3 of the lamina propria dendritic cells (LPDCs). The regulatory effect of C. butyricum was verified in bone marrowderived dendritic cells by in vitro experiments. RESULTS The secretion of proinflammatory cytokines (IL-1β and IL-6) in mice with IBS was significantly increased compared with that of the control group, which suggested that the intestinal mucosa in mice with IBS was in a low-grade inflammatory state. The expression of CD11C+CD80+ and CD11c+TIM3+ in intestinal LPDCs in mice with IBS increased significantly. Meanwhile, the cytokines (IL-1β and IL-6展开更多
目的探讨初诊肺结核患者血浆白细胞介素-6(IL-6)、白细胞介素-17(IL-17)、白细胞介素-37(IL-37)及T细胞免疫球蛋白黏蛋白分子-3(TIM-3)水平变化及其临床意义。方法收集2018年1月~2020年10月百色市人民医院收治的活动性肺结核患者57例、...目的探讨初诊肺结核患者血浆白细胞介素-6(IL-6)、白细胞介素-17(IL-17)、白细胞介素-37(IL-37)及T细胞免疫球蛋白黏蛋白分子-3(TIM-3)水平变化及其临床意义。方法收集2018年1月~2020年10月百色市人民医院收治的活动性肺结核患者57例、肺炎患者50例和健康对照40例。57例肺结核患者中菌阳肺结核31例,菌阴肺结核26例。57例肺结核按病情轻重、病程长短及病变范围分为轻症组32例和重症组25例。采用酶联免疫吸附测定(ELISA)法检测各组血浆IL-6,IL-17,IL-37及TIM-3水平,并进行比较。结果肺结核组血浆IL-6(41.37±13.50 pg/ml vs 26.28±9.16pg/ml,3.05±1.08 pg/ml),IL-17(62.50±10.73pg/ml vs 30.47±7.18pg/ml,16.13±5.86pg/ml),IL-37(14.63±4.18pg/ml vs 9.85±2.74pg/ml,4.10±1.02 pg/ml)及TIM-3(18.17±5.16ng/ml vs 11.80±3.52ng/ml,6.24±2.15 ng/ml)水平均明显高于肺炎组和对照组,差异均有统计学意义(t=7.338~13.273,均P<0.001)。菌阳肺结核组血浆IL-6(52.60±15.71pg/ml vs 30.16±8.95 pg/ml),IL-17(72.35±15.20 pg/ml vs 46.52±9.13 pg/ml),IL-37(16.50±6.14 pg/ml vs 12.48±3.17 pg/ml)及TIM-3(21.70±7.93ng/ml vs 15.21±4.92 ng/ml)水平均明显高于菌阴肺结核组,差异具有统计学意义(t=8.472,10.161,6.925,9.106,均P<0.001)。重症组血浆IL-6(56.38±17.26pg/ml vs 25.84±9.27pg/ml),IL-17(79.50±16.38 pg/ml vs 48.20±8.74 pg/ml),IL-37(18.48±6.20 pg/ml vs 10.82±3.26pg/ml)及TIM-3(23.26±8.15ng/ml vs 13.90±4.71ng/ml)水平明显高于轻症组,差异具有统计学意义(t=12.642,14.513,10.205,13.172,均P<0.001)。结论血浆IL-6,IL-17,IL-37及TIM-3水平在肺结核患者中明显升高,对判断肺结核严重程度有一定的价值。展开更多
目的探讨T细胞免疫球蛋白和黏蛋白结构域分子3(T cell immunoglobulin and mucin domain protein 3,Tim-3)在晚期血吸虫病患者外周血CD56+自然杀伤细胞(NK细胞)表面的表达及其与肝纤维化指标的关系。方法采用流式细胞术检测28例临床晚...目的探讨T细胞免疫球蛋白和黏蛋白结构域分子3(T cell immunoglobulin and mucin domain protein 3,Tim-3)在晚期血吸虫病患者外周血CD56+自然杀伤细胞(NK细胞)表面的表达及其与肝纤维化指标的关系。方法采用流式细胞术检测28例临床晚期血吸虫病患者和30例健康者CD56+NK细胞表面Tim-3的表达,应用全自动化学发光免疫分析仪检测肝纤维化血清学三型前胶原N端肽(PIIIP N-P)、层黏连蛋白(LN)、IV型胶原(CIV)和透明质酸(HA)等4项指标,ELISA检测血清中γ-干扰素(IFN-γ)和白细胞介素-4(IL-4)水平,Fibroscan仪检测肝硬度值(LSM)反映肝纤维化程度。统计分析Tim-3表达水平与IL-4和IFN-γ水平、肝脏纤维化程度以及肝纤维化血清指标的相关性。结果流式细胞分析结果显示,晚期血吸虫病患者外周血CD56+NK细胞表面Tim-3表达水平为(62.3±11.4)%,高于健康对照组的(52.1±6.5)%(P<0.01)。晚期血吸虫病患者和健康对照组的PIIIP N-P水平分别为(86.5±29.5)ng/ml和(22.0±7.8)ng/ml,LN分别为(49.3±21.5)ng/ml和(20.4±6.3)ng/ml,CIV分别为(67.5±22.3)ng/ml和(22.0±3.9)ng/ml,HA分别为(645.9±483.1)ng/ml和(54.7±27.7)ng/ml,两组各指标差异均具有统计学意义(P<0.05)。晚期血吸虫病患者和健康对照组IFN-γ水平分别为(93.9±20.1)ng/L和(107.7±24.6)ng/L,IL-4分别为(46.6±11.8)ng/L和(28.9±8.9)ng/L,两组差异均具有统计学意义(P<0.05)。Spearman非参数相关分析结果显示患者CD56+NK细胞表达的Tim-3水平与患者肝纤维化指标LSM、PIIIP N-P、LN、CIV和IL-4水平呈正相关(r=0.528~0.834,P<0.01),与IFN-γ水平呈负相关(r=-0.501,P<0.01),而与HA水平无明显相关性(r=0.352,P>0.05)。结论晚期血吸虫病患者外周血CD56+NK细胞Tim-3表达呈上调,并与患者肝纤维化指标LSM、PIIIP N-P、LN、CIV和IL-4水平呈正相关。展开更多
基金supported by grants from National Natural Science Foundation of China (No. 30700799, 81172803)Doctoral Fund of Ministry of Education of China (No. 20070487119)Natural Science Foundation of Hubei Province (No. 2007AD A201)
文摘T cell immunoglobulin and mucin domain 3 （Tim-3） is well known to negatively regulate T cells responses, but its role in burn-induced T cells immune suppression remains unclear. In the present study, in order to identify the relationship between Tim-3 expression and post-burn T cells immune suppression, C57BL/6 mice were subjected to burn injury or sham injury, and the liver and spleen were harvested at the day 1 after operation. The expression level of Tim-3 on hepatic or splenic T cells and the functional properties of Tim-3＋ T cells were evaluated. It was found burn injury induced dramatically elevated Tim-3 expression on both hepatic and splenic CD4＋ and CD8＋ T cells in contrast with the post-burn depletion of T cells. Furthermore, Tim-3 expression was correlated with the suppressive phenotype of T cells following burn injury, including increased expression of anti-inflammatory cytokine IL-10, decreased expression of pro-inflammatory cytokines IFN-γ and TNF-α, reduced T cell proliferation and elevated co-expression of Tim-3 and PD-1. Moreover, Tim-3＋ T cells subsets were more prone to spontaneous apoptosis than Tim-3- T cells subsets. Our findings reinforce the idea that the up-regulated expression of Tim-3 on T cells after burn injury plays an important role in the development and maintenance of burn-induced T cell immune suppression.
基金Supported by the National Natural Science Foundation of China,No.81770538 and No.81570485Key Research and Development Program of Shandong Province,No.2017CXGC1215
文摘BACKGROUND Irritable bowel syndrome (IBS) is one of the most common functional gastroenterological diseases characterized by abnormal visceral sensitivity and lowgrade inflammation. The role of Clostridium butyricum (C. butyricum) in reducing intestinal low-grade inflammation via immune pathways has been well defined. However, the detailed mechanisms of the effects of C. butyricum on intestinal mucosal immunity, especially on immune cells of the lamina propria, remain unclear. Dendritic cells (DCs), which are important immune cells, secrete proinflammatory cytokines (IL-1β, IL-6, and others) and express T cell immunoglobulin and mucin domain-3 (TIM3), promoting proliferation and activation of DCs, and mediating Th1 and Th17 inflammatory responses. AIM To investigate the role of DCs in the development of IBS in a rat model and to understand the regulation of DCs after C. butyricum intervention. METHODS An IBS animal model was established using C57BL/6 mice, and C. butyricum was continuously administered via the intragastric route to simulate different intestinal immune states. Intestinal visceral hypersensitivity and histopathology were assessed using the abdominal withdrawal reflex (AWR) test and hematoxylin & eosin (H&E) staining, respectively. The expression of proinflammatory cytokines (IL-1β and IL-6) and TIM3 was analyzed by Western blot analysis and real-time PCR. Flow cytometry was applied to analyze the quantity, function, and membrane molecule TIM3 of the lamina propria dendritic cells (LPDCs). The regulatory effect of C. butyricum was verified in bone marrowderived dendritic cells by in vitro experiments. RESULTS The secretion of proinflammatory cytokines (IL-1β and IL-6) in mice with IBS was significantly increased compared with that of the control group, which suggested that the intestinal mucosa in mice with IBS was in a low-grade inflammatory state. The expression of CD11C+CD80+ and CD11c+TIM3+ in intestinal LPDCs in mice with IBS increased significantly. Meanwhile, the cytokines (IL-1β and IL-6
文摘目的探讨初诊肺结核患者血浆白细胞介素-6(IL-6)、白细胞介素-17(IL-17)、白细胞介素-37(IL-37)及T细胞免疫球蛋白黏蛋白分子-3(TIM-3)水平变化及其临床意义。方法收集2018年1月~2020年10月百色市人民医院收治的活动性肺结核患者57例、肺炎患者50例和健康对照40例。57例肺结核患者中菌阳肺结核31例,菌阴肺结核26例。57例肺结核按病情轻重、病程长短及病变范围分为轻症组32例和重症组25例。采用酶联免疫吸附测定(ELISA)法检测各组血浆IL-6,IL-17,IL-37及TIM-3水平,并进行比较。结果肺结核组血浆IL-6(41.37±13.50 pg/ml vs 26.28±9.16pg/ml,3.05±1.08 pg/ml),IL-17(62.50±10.73pg/ml vs 30.47±7.18pg/ml,16.13±5.86pg/ml),IL-37(14.63±4.18pg/ml vs 9.85±2.74pg/ml,4.10±1.02 pg/ml)及TIM-3(18.17±5.16ng/ml vs 11.80±3.52ng/ml,6.24±2.15 ng/ml)水平均明显高于肺炎组和对照组,差异均有统计学意义(t=7.338~13.273,均P<0.001)。菌阳肺结核组血浆IL-6(52.60±15.71pg/ml vs 30.16±8.95 pg/ml),IL-17(72.35±15.20 pg/ml vs 46.52±9.13 pg/ml),IL-37(16.50±6.14 pg/ml vs 12.48±3.17 pg/ml)及TIM-3(21.70±7.93ng/ml vs 15.21±4.92 ng/ml)水平均明显高于菌阴肺结核组,差异具有统计学意义(t=8.472,10.161,6.925,9.106,均P<0.001)。重症组血浆IL-6(56.38±17.26pg/ml vs 25.84±9.27pg/ml),IL-17(79.50±16.38 pg/ml vs 48.20±8.74 pg/ml),IL-37(18.48±6.20 pg/ml vs 10.82±3.26pg/ml)及TIM-3(23.26±8.15ng/ml vs 13.90±4.71ng/ml)水平明显高于轻症组,差异具有统计学意义(t=12.642,14.513,10.205,13.172,均P<0.001)。结论血浆IL-6,IL-17,IL-37及TIM-3水平在肺结核患者中明显升高,对判断肺结核严重程度有一定的价值。
文摘目的:探究T细胞免疫球蛋白黏液素(T cell immunoglobulin and mucin,Tim)3在再生障碍性贫血(aplastic anemia,AA)和骨髓增生异常综合征(myelodysplastic syndrome,MDS)鉴别诊断中的意义。方法:流式细胞术检测24例AA患者、20例MDS患者和17例健康对照者外周血单个核细胞(peripheral blood mononuclear cells,PBMC)中CD4^+Tim1^+和CD4^+Tim3^+细胞比例。实时荧光定量PCR检测AA、MDS患者和健康对照者PBMC中Tim3 m RNA和S型凝集素半乳糖凝集素9(galectin-9,Gal-9)mRNA表达水平。结果:健康对照者、AA和MDS患者PBMC中CD4^+Tim1^+细胞比例差异无统计学意义;MDS患者的CD4^+Tim3^+细胞比例明显高于AA患者和健康对照者(P<0.05);高危组MDS患者CD4^+Tim3^+细胞比例明显高于低中危组MDS患者(P<0.01)和健康对照者(P<0.05);健康对照者、AA和MDS患者的Tim3 m RNA和Gal-9 mRNA水平差异无统计学意义。结论:MDS患者Tim3表达水平明显高于AA患者,并与疾病危险度有关,提示Tim3可能参与MDS的发病,并可能成为临床鉴别AA与MDS的标志物。
