慢性鼻—鼻窦炎伴息肉患者AhR表达与Th17反应相关性及AhR配体干预的研究
发布时间：2018-08-20 07:49
【摘要】：慢性鼻-鼻窦炎伴息肉(chronic rhinosinusitis with nasal polyps, CRSwNP)是耳鼻咽喉科临床上常见的、多发的鼻腔和鼻窦粘膜的慢性炎症性疾病。根据目前的流行病学调查显示，CRSwNP在全球范围内的发病率已高达2~5%，，其发生严重影响患者的生活和睡眠质量及工作效率，已成为人类主要的公共卫生问题之一，同时也带来了严重的经济负担。虽然CRSwNP目前的诊疗水平已经大幅度提高，但是其治疗效果依然不能令所有患者满意，且治疗后复发率较高。在既往数十年，临床耳鼻喉科医生及科研工作者对CRSwNP的病因、发病机制和治疗进行了深入而广泛的探索和研究。目前认为，CRSwNP患者鼻腔和鼻窦粘膜的慢性炎症主要是由诸如解剖结构异常、感染、变应性体质、免疫调节功能异常等单个或多个因素共同作用所致，其中Th17反应亢进导致的以Th17细胞过度活化及其相应的相关促炎细胞因子的大量释放是造成国人CRSwNP发生发展的重要原因。 芳香烃受体(aryl hydrocarbon receptor, AhR)，一种依靠配体激活的转录因子，在调节人体免疫反应中发挥了重要作用。已有研究表明它参与了哮喘、特应性皮炎、实验性自身免疫性脑脊髓炎和类风湿性关节炎等过敏性和自身免疫性疾病的发病机制。近期的动物实验也显示AhR可通过控制T淋巴细胞和树突细胞（dendritic cells, DCs)的分化从而发挥强大的免疫调节能力。尤其值得注意的是，AhR一旦被它的天然配体诸如2-（1-吲哚-3-羰基）-噻唑-4-羧酸甲酯(2-(1H-indole-3-carbonyl)-thiazole-4-carboxylic acid methyl ester, ITE)激活，它就能抑制Th17反应，进而控制慢性炎症。因此，我们假设AhR可能参与了CRSwNP患者慢性炎症的形成。 本实验的目的是探索AhR在伴变应性体质和不伴变应性体质的CRSwNP患者发病中的作用及其与CRSwNP患者Th17反应的相关性，并予以ITE体外干预CRSwNP患者和健康对照来源的免疫细胞，探讨AhR-DC-Th17信号通路存在的意义，从而寻找到可能治疗该疾病的新的靶点。第一部分CRSwNP患者鼻息肉组织和外周血AhR与Th17反应 相关性研究 目的：通过检测AhR在鼻息肉组织和外周血的表达，分析其与患者全身及局部Th17反应的相关性，评估在CRSwNP患者中AhR对Th17反应的调节能力，为深入阐明CRSwNP的发病机制及为治疗该疾病找到新的靶点提供相应的理论依据。 方法：收集48例CRSwNP患者（伴变应性体质组/atopic组24例；不伴变应性体质组/non-atopic组24例）的鼻息肉和外周血标本和13例脑脊液鼻漏患者（对照组）的下鼻甲粘膜和外周血标本。检测AhR (RT-qPCR及Western blot检测法)、RORC (RT-qPCR检测法)、IL-17和IL-10(ELISA检测法)的表达水平及Th17细胞的比率(流式细胞术)。 结果：CRSwNP患者鼻息肉组织和外周血中AhR的表达水平较对照组显著降低，且atopic组的表达水平较non-atopic组更低，差异有统计学意义；然而，CRSwNP患者鼻息肉组织RORC水平较对照组显著升高，外周血Th17细胞及IL-17水平亦较对照组明显升高，且三者在atopic组的水平均较non-atopic组更高，差异具有统计学意义。CRSwNP患者鼻息肉组织AhR表达水平与RORC及IL-17水平均呈负相关，外周血AhR表达水平与Th17比率及IL-17水平亦呈负相关；而CRSwNP患者鼻息肉组织AhR水平与外周血AhR水平呈高度正相关，鼻息肉组织RORC及IL-17水平与外周血Th17比率及IL-17水平亦呈高度正相关。 结论：AhR的表达降低及过度的Th17反应存在于CRSwNP患者的鼻息肉组织及外周血中，由于AhR表达的降低而引起的鼻息肉组织及外周血的Th17反应在CRSwNP患者的发病机制中可能扮演着重要的角色；而atopic组表现为更低的AhR表达及更严重的Th17反应，提示变应性因素可能通过降低AhR表达从而加剧Th17反应。 第二部分AhR配体对CRSwNP患者PBMCs中Th17反应的干预调控研究 目的：通过将AhR配体ITE作为干预手段，观察ITE干预的两组CRSwNP患者PBMCs中AhR表达、Th17比率、IL-17和IL-10水平的变化情况，分析AhR-Th17及其相关细胞因子在CRSwNP发生发展中所扮演的角色，并在前一部分实验基础上，体外证实AhR配体ITE可抑制CRSwNP患者的Th17反应，从而达到在一定程度上控制炎症的目的。 方法：收集18例CRSwNP患者（atopic组9例；non-atopic组9例）和9例脑脊液鼻漏的外周血标本，分离得到PBMCs后予以ITE干预。采用Western blot检测两组CRSwNP患者PBMCs中AhR表达水平；采用流式细胞术检测PBMCs中Th17细胞比率；采用ELISA检测PBMCs培养上清液中IL-17及IL-10的水平。 结果：通过ITE干预后，两组CRSwNP患者PBMCs中AhR表达均升高，而Th17细胞比率和IL-17水平则显著降低。此外，IL-10的水平在ITE干预后显著升高。 结论：AhR的表达可在ITE的作用下升高，并参与抑制Th17反应和促进IL-10的产生，揭示了AhR在调控Th17反应中发挥着负调节子的功能，证实了ITE可通过AhR-Th17信号通路抑制CRSwNP患者的炎症反应。 第三部分树突细胞和T细胞中AhR及相关细胞因子的表达水平的研究 目的：通过检测两组CRSwNP患者及健康对照组外周血来源的DCs和CD4+T细胞AhR表达及相关细胞因子的分泌水平，以期找到免疫调节过程中AhR作用的靶点。 方法：收集18例CRSwNP患者（atopic组9例；non-atopic组9例）和9例健康成年人的外周血标本，通过各自磁珠分选得到单核细胞和CD4+T细胞；一方面将单核细胞通过培养7天诱导为DCs；另一方面直接将分选的CD4+T细胞培养3天。采用RT-qPCR和Western Blot方法检测DCs和CD4+T细胞AhR的表达；；采用ELISA检测细胞培养上清液中IL-1β、IL-6、IL-10、和IL-17的水平。 结果：CRSwNP患者DCs中AhR的表达水平较对照组显著降低，且atopic组的表达水平较non-atopic组更低，差异有统计学意义；而三组的CD4+T细胞AhR表达无明显差异，经过统计学分析差异无意思。CRSwNP患者DCs分泌促炎性细胞因子IL-1β和IL-6增加，同时抗炎性细胞因子IL-10的分泌减少；而CRSwNP患者CD4+T细胞分泌促炎性细胞因子IL-17增高，而抗炎性细胞因子IL-10的分泌降低；且atopic CRSwNP患者组和Non-atopic CRSwNP患者组细胞因子水平均存在明显的统计学差异。 结论：我们的研究表明DCs中AhR的缺陷可能是导致Th17反应的靶点，AhR在DCs的活化可能在调控抗炎反应中起关键作用。此外，AhR的缺陷在伴有atopy的CRSwNP患者更加严重，这也提示我们变应性因素可能也是通过AhR信号通路进而加重CRSwNP患者的Th17反应。 第四部分AhR配体通过干预树突细胞和T细胞抑制CRSwNP患者的Th17反应 目的：通过AhR配体ITE干预两组CRSwNP患者外周血来源的DCs和CD4+T细胞，分析ITE通过AhR-DCs-CD4+T细胞轴和AhR-CD4+T细胞轴对Th17反应的影响。 方法：收集20例CRSwNP患者（atopic组10例；non-atopic组10例）和12例健康成年人的外周血标本，通过各自磁珠分选得到单核细胞和CD4+T细胞；一方面将单核细胞诱导为DCs，并予以ITE干预后与CD4+T细胞共培养；另一方面直接予以ITE干预CD4+T细胞。采用RT-qPCR方法检测DCs和CD4+T细胞AhR的表达；采用流式细胞术检测Th17细胞比率；采用ELISA检测细胞培养上清液中IL-1β、IL-6、IL-10、和IL-17的水平。 结果：予以ITE干预DCs后,能显著抑制DCs分泌促炎性细胞因子IL-1β和IL-6的分泌，同时促进抗炎性细胞因子IL-10的分泌；予以ITE干预CD4+T细胞后，能明显抑制CD4+T细胞分泌促炎性细胞因子IL-17和促进抗炎性细胞因子IL-10的分泌；同时抑制Th17细胞的分化。 结论：ITE可通过作用于DCs和CD4+T细胞从而抑制Th17反应并控制CRSwNP患者的炎症反应；AhR-DCs-Th17细胞轴可能是治疗CRSwNP患者的重要信号通路。ITE作为一种无毒的AhR配体，能够在体外明显抑制CRSwNP患者的Th17反应，因此，它将来可能成为治疗CRSwNP患者的潜在候选药物。
[Abstract]:Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common chronic inflammatory disease of the nasal cavity and sinus mucosa in otolaryngology. According to the current epidemiological investigation, the incidence of CRSwNP in the world has reached 2-5%, which seriously affects the lives and lives of patients. Sleep quality and work efficiency have become one of the major public health problems of mankind, but also brought serious economic burden. Although the level of diagnosis and treatment of CRSwNP has been greatly improved, its treatment effect is still unsatisfactory to all patients, and the recurrence rate after treatment is high. In the past decades, clinical otolaryngologists At present, it is believed that the chronic inflammation of nasal cavity and sinus mucosa in CRSwNP patients is mainly caused by single or multiple factors such as abnormal anatomy, infection, allergic constitution, and abnormal immune regulation, among which Th17 The overactivation of Th17 cells and the release of inflammatory cytokines are the important reasons for the development of CRSwNP in Chinese.
Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, plays an important role in regulating human immune response. It has been shown to be involved in the pathogenesis of allergic and autoimmune diseases such as asthma, atopic dermatitis, experimental autoimmune encephalomyelitis and rheumatoid arthritis. Recent animal studies have also shown that AhR exerts powerful immune regulation by controlling the differentiation of T lymphocytes and dendritic cells (DCs). It is particularly noteworthy that once AhR is subjected to its natural ligands such as 2-(1-indole-3-carbonyl) -thiazole-4-carboxylic acid methyl ester (2-(1H-indole-3-carbonyl) -thiazole-4-carb Activation of oxylic acid methyl ester (ITE) can inhibit Th17 response and thus control chronic inflammation. Therefore, we hypothesize that AhR may be involved in the formation of chronic inflammation in CRSwNP patients.
The purpose of this study was to explore the role of AhR in the pathogenesis of CRSwNP patients with allergic constitution and non-allergic constitution and its correlation with Th17 reaction in CRSwNP patients. ITE was given to intervene in vitro the immune cells from CRSwNP patients and healthy controls, and to explore the significance of AhR-DC-Th17 signaling pathway in order to find possible treatment. The new target of the disease. Part I: AhR and Th17 reaction in nasal polyps and peripheral blood of CRSwNP patients
Correlation study
AIM: To investigate the expression of AhR in nasal polyps and peripheral blood, analyze its correlation with systemic and local Th17 response, and evaluate the regulation of AhR on Th17 response in patients with CRSwNP.
Methods: 48 patients with CRSwNP (24 patients with allergic constitution / atopic group; 24 patients without allergic constitution / non-atopic group) and 13 patients with cerebrospinal fluid rhinorrhea (control group) were collected for nasal polyps and peripheral blood samples. The expression level of IL-10 (ELISA assay) and the ratio of Th17 cells (flow cytometry).
Results: The expression level of AhR in nasal polyps and peripheral blood of CRSwNP patients was significantly lower than that of control group, and the expression level of AhR in atopic group was lower than that of non-atopic group. However, the RORC level in nasal polyps of CRSwNP patients was significantly higher than that of control group, and the levels of Th17 cells and IL-17 in peripheral blood were also significantly higher than that of control group. The expression of AhR in nasal polyps of CRSwNP patients was negatively correlated with RORC and IL-17 levels, and the expression of AhR in peripheral blood was negatively correlated with Th17 ratio and IL-17 level, while the level of AhR in nasal polyps of CRSwNP patients was negatively correlated with that in peripheral blood. RORC and IL-17 levels in nasal polyps were positively correlated with Th17 ratio and IL-17 level in peripheral blood.
CONCLUSION: Decreased AhR expression and excessive Th17 reaction are present in nasal polyps and peripheral blood of CRSwNP patients. Th17 reaction in nasal polyps and peripheral blood may play an important role in the pathogenesis of CRSwNP patients caused by decreased AhR expression, whereas lower expression and more severe Th17 reaction may be found in atopic patients. The Th17 reaction suggests that allergic factors may aggravate the Th17 response by decreasing the expression of AhR.
The second part is the intervention and regulation of AhR ligand on Th17 response in PBMCs of CRSwNP patients.
AIM: To observe the changes of AhR expression, Th17 ratio, IL-17 and IL-10 levels in PBMCs of two groups of CRSwNP patients treated with ITE, and to analyze the role of AhR-Th17 and its related cytokines in the development of CRSwNP. The Th17 reaction of SwNP patients can achieve the purpose of controlling inflammation to some extent.
Methods: 18 patients with CRSwNP (9 in atopic group, 9 in non-atopic group) and 9 patients with cerebrospinal fluid rhinorrhea (CSF rhinorrhea) were collected. PBMCs were isolated and treated with ITE. The expression of AhR in PBMCs was detected by Western blot, the Th17 cell ratio in PBMCs was detected by flow cytometry, and the PBMCs culture was detected by ELISA. The level of IL-17 and IL-10 in clear liquid.
Results: After ITE intervention, the expression of AhR in PBMCs of CRSwNP patients in both groups increased, while the ratio of Th17 cells and the level of IL-17 decreased significantly. In addition, the level of IL-10 increased significantly after ITE intervention.
CONCLUSION: The expression of AhR can be elevated under the action of ITE, and is involved in inhibiting Th17 response and promoting IL-10 production. It reveals that AhR plays a negative regulatory role in regulating Th17 response, which confirms that ITE can inhibit inflammation in CRSwNP patients through AhR-Th17 signaling pathway.
The third part is the expression level of AhR and related cytokines in dendritic cells and T cells.
AIM: To detect the expression of AhR and the secretion of cytokines in peripheral blood-derived DCs and CD4 + T cells from CRSwNP patients and healthy controls in order to find the target of AhR in the process of immunoregulation.
Methods: Monocytes and CD4 + T cells were isolated from peripheral blood samples of 18 patients with CRSwNP (9 cases in atopic group, 9 cases in non-atopic group) and 9 healthy adults by magnetic beads sorting. Monocytes were induced into DCs after 7 days of culture, and CD4 + T cells were cultured directly for 3 days. RT-qPCR and Western B PCR were used. The expression of AhR in DCs and CD4+T cells was detected by lot assay
Results: The expression level of AhR in DCs of CRSwNP patients was significantly lower than that of control group, and the expression level of AhR in atopic group was lower than that of non-atopic group, the difference was statistically significant; but the expression of AhR in CD4 + T cells of three groups was not significantly different, and the difference was insignificant after statistical analysis. The secretion of anti-inflammatory cytokine IL-10 decreased, while that of pro-inflammatory cytokine IL-17 and anti-inflammatory cytokine IL-10 increased in CD4+T cells of CRSwNP patients and decreased in non-atopic CRSwNP patients.
CONCLUSION: Our study suggests that the deficiency of AhR in DCs may be the target of Th17 reaction, and the activation of AhR in DCs may play a key role in regulating anti-inflammatory response. In addition, the deficiency of AhR is more serious in CRSWNP patients with atopy, suggesting that allergic factors may also aggravate CRSwNP through AhR signaling pathway. The Th17 reaction.
The fourth part of the AhR ligand inhibits the Th17 response in CRSwNP patients by interfering with dendritic cells and T cells.
AIM: To investigate the effects of AhR ligand ITE on the Th17 response of peripheral blood-derived DCs and CD4 + T cells in two groups of CRSwNP patients.
Methods: Twenty patients with CRSwNP (10 patients in atopic group; 10 patients in non-atopic group) and twelve healthy adults were collected. Monocytes and CD4 + T cells were isolated by magnetic beads. Monocytes were induced into DCs and co-cultured with CD4 + T cells after ITE intervention. The expression of AhR in DCs and CD4+T cells was detected by RT-q PCR, the ratio of Th17 cells was detected by flow cytometry, and the levels of IL-1beta, IL-6, IL-10 and IL-17 in the supernatant were detected by ELISA.
Results: ITE could significantly inhibit the secretion of pro-inflammatory cytokines IL-1beta and IL-6, and promote the secretion of anti-inflammatory cytokines IL-10. ITE could significantly inhibit the secretion of pro-inflammatory cytokine IL-17 and anti-inflammatory cytokine IL-Th10 in CD4+T cells. 7 cell differentiation.
CONCLUSION: ITE can inhibit Th17 reaction and control inflammation in CRSwNP patients by acting on DCs and CD4+T cells, and the AhR-DCs-Th17 cell axis may be an important signaling pathway in the treatment of CRSwNP patients. Potential candidate drugs for CRSwNP patients.
【学位授予单位】：重庆医科大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R765.21
本文编号：2192928
[Abstract]:Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common chronic inflammatory disease of the nasal cavity and sinus mucosa in otolaryngology. According to the current epidemiological investigation, the incidence of CRSwNP in the world has reached 2-5%, which seriously affects the lives and lives of patients. Sleep quality and work efficiency have become one of the major public health problems of mankind, but also brought serious economic burden. Although the level of diagnosis and treatment of CRSwNP has been greatly improved, its treatment effect is still unsatisfactory to all patients, and the recurrence rate after treatment is high. In the past decades, clinical otolaryngologists At present, it is believed that the chronic inflammation of nasal cavity and sinus mucosa in CRSwNP patients is mainly caused by single or multiple factors such as abnormal anatomy, infection, allergic constitution, and abnormal immune regulation, among which Th17 The overactivation of Th17 cells and the release of inflammatory cytokines are the important reasons for the development of CRSwNP in Chinese.
Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, plays an important role in regulating human immune response. It has been shown to be involved in the pathogenesis of allergic and autoimmune diseases such as asthma, atopic dermatitis, experimental autoimmune encephalomyelitis and rheumatoid arthritis. Recent animal studies have also shown that AhR exerts powerful immune regulation by controlling the differentiation of T lymphocytes and dendritic cells (DCs). It is particularly noteworthy that once AhR is subjected to its natural ligands such as 2-(1-indole-3-carbonyl) -thiazole-4-carboxylic acid methyl ester (2-(1H-indole-3-carbonyl) -thiazole-4-carb Activation of oxylic acid methyl ester (ITE) can inhibit Th17 response and thus control chronic inflammation. Therefore, we hypothesize that AhR may be involved in the formation of chronic inflammation in CRSwNP patients.
The purpose of this study was to explore the role of AhR in the pathogenesis of CRSwNP patients with allergic constitution and non-allergic constitution and its correlation with Th17 reaction in CRSwNP patients. ITE was given to intervene in vitro the immune cells from CRSwNP patients and healthy controls, and to explore the significance of AhR-DC-Th17 signaling pathway in order to find possible treatment. The new target of the disease. Part I: AhR and Th17 reaction in nasal polyps and peripheral blood of CRSwNP patients
Correlation study
AIM: To investigate the expression of AhR in nasal polyps and peripheral blood, analyze its correlation with systemic and local Th17 response, and evaluate the regulation of AhR on Th17 response in patients with CRSwNP.
Methods: 48 patients with CRSwNP (24 patients with allergic constitution / atopic group; 24 patients without allergic constitution / non-atopic group) and 13 patients with cerebrospinal fluid rhinorrhea (control group) were collected for nasal polyps and peripheral blood samples. The expression level of IL-10 (ELISA assay) and the ratio of Th17 cells (flow cytometry).
Results: The expression level of AhR in nasal polyps and peripheral blood of CRSwNP patients was significantly lower than that of control group, and the expression level of AhR in atopic group was lower than that of non-atopic group. However, the RORC level in nasal polyps of CRSwNP patients was significantly higher than that of control group, and the levels of Th17 cells and IL-17 in peripheral blood were also significantly higher than that of control group. The expression of AhR in nasal polyps of CRSwNP patients was negatively correlated with RORC and IL-17 levels, and the expression of AhR in peripheral blood was negatively correlated with Th17 ratio and IL-17 level, while the level of AhR in nasal polyps of CRSwNP patients was negatively correlated with that in peripheral blood. RORC and IL-17 levels in nasal polyps were positively correlated with Th17 ratio and IL-17 level in peripheral blood.
CONCLUSION: Decreased AhR expression and excessive Th17 reaction are present in nasal polyps and peripheral blood of CRSwNP patients. Th17 reaction in nasal polyps and peripheral blood may play an important role in the pathogenesis of CRSwNP patients caused by decreased AhR expression, whereas lower expression and more severe Th17 reaction may be found in atopic patients. The Th17 reaction suggests that allergic factors may aggravate the Th17 response by decreasing the expression of AhR.
The second part is the intervention and regulation of AhR ligand on Th17 response in PBMCs of CRSwNP patients.
AIM: To observe the changes of AhR expression, Th17 ratio, IL-17 and IL-10 levels in PBMCs of two groups of CRSwNP patients treated with ITE, and to analyze the role of AhR-Th17 and its related cytokines in the development of CRSwNP. The Th17 reaction of SwNP patients can achieve the purpose of controlling inflammation to some extent.
Methods: 18 patients with CRSwNP (9 in atopic group, 9 in non-atopic group) and 9 patients with cerebrospinal fluid rhinorrhea (CSF rhinorrhea) were collected. PBMCs were isolated and treated with ITE. The expression of AhR in PBMCs was detected by Western blot, the Th17 cell ratio in PBMCs was detected by flow cytometry, and the PBMCs culture was detected by ELISA. The level of IL-17 and IL-10 in clear liquid.
Results: After ITE intervention, the expression of AhR in PBMCs of CRSwNP patients in both groups increased, while the ratio of Th17 cells and the level of IL-17 decreased significantly. In addition, the level of IL-10 increased significantly after ITE intervention.
CONCLUSION: The expression of AhR can be elevated under the action of ITE, and is involved in inhibiting Th17 response and promoting IL-10 production. It reveals that AhR plays a negative regulatory role in regulating Th17 response, which confirms that ITE can inhibit inflammation in CRSwNP patients through AhR-Th17 signaling pathway.
The third part is the expression level of AhR and related cytokines in dendritic cells and T cells.
AIM: To detect the expression of AhR and the secretion of cytokines in peripheral blood-derived DCs and CD4 + T cells from CRSwNP patients and healthy controls in order to find the target of AhR in the process of immunoregulation.
Methods: Monocytes and CD4 + T cells were isolated from peripheral blood samples of 18 patients with CRSwNP (9 cases in atopic group, 9 cases in non-atopic group) and 9 healthy adults by magnetic beads sorting. Monocytes were induced into DCs after 7 days of culture, and CD4 + T cells were cultured directly for 3 days. RT-qPCR and Western B PCR were used. The expression of AhR in DCs and CD4+T cells was detected by lot assay
Results: The expression level of AhR in DCs of CRSwNP patients was significantly lower than that of control group, and the expression level of AhR in atopic group was lower than that of non-atopic group, the difference was statistically significant; but the expression of AhR in CD4 + T cells of three groups was not significantly different, and the difference was insignificant after statistical analysis. The secretion of anti-inflammatory cytokine IL-10 decreased, while that of pro-inflammatory cytokine IL-17 and anti-inflammatory cytokine IL-10 increased in CD4+T cells of CRSwNP patients and decreased in non-atopic CRSwNP patients.
CONCLUSION: Our study suggests that the deficiency of AhR in DCs may be the target of Th17 reaction, and the activation of AhR in DCs may play a key role in regulating anti-inflammatory response. In addition, the deficiency of AhR is more serious in CRSWNP patients with atopy, suggesting that allergic factors may also aggravate CRSwNP through AhR signaling pathway. The Th17 reaction.
The fourth part of the AhR ligand inhibits the Th17 response in CRSwNP patients by interfering with dendritic cells and T cells.
AIM: To investigate the effects of AhR ligand ITE on the Th17 response of peripheral blood-derived DCs and CD4 + T cells in two groups of CRSwNP patients.
Methods: Twenty patients with CRSwNP (10 patients in atopic group; 10 patients in non-atopic group) and twelve healthy adults were collected. Monocytes and CD4 + T cells were isolated by magnetic beads. Monocytes were induced into DCs and co-cultured with CD4 + T cells after ITE intervention. The expression of AhR in DCs and CD4+T cells was detected by RT-q PCR, the ratio of Th17 cells was detected by flow cytometry, and the levels of IL-1beta, IL-6, IL-10 and IL-17 in the supernatant were detected by ELISA.
Results: ITE could significantly inhibit the secretion of pro-inflammatory cytokines IL-1beta and IL-6, and promote the secretion of anti-inflammatory cytokines IL-10. ITE could significantly inhibit the secretion of pro-inflammatory cytokine IL-17 and anti-inflammatory cytokine IL-Th10 in CD4+T cells. 7 cell differentiation.
CONCLUSION: ITE can inhibit Th17 reaction and control inflammation in CRSwNP patients by acting on DCs and CD4+T cells, and the AhR-DCs-Th17 cell axis may be an important signaling pathway in the treatment of CRSwNP patients. Potential candidate drugs for CRSwNP patients.
【学位授予单位】：重庆医科大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R765.21
【共引文献】
相关期刊论文 前10条
1 王海树;袁红海;潘三强;宿宝贵;;TCDD宫内暴露对子鼠肝细胞和亚细胞结构的毒性作用[J];解剖学研究;2013年04期
2 Gui-lin Yang;Ying-xia Liu;Mu-tong Fang;Wei-long Liu;Xin-chun Chen;John Nunnari;Jing-jing Xie;Ming-feng Liao;Ming-xia Zhang;Guo-bao Li;Pei-ze Zhang;Yi Guan;Bo-ping Zhou;;Higher Viral Load and Prolonged Viral Shedding Period is Associated with Impaired Th17 Cell Response in Patients with H1N1 Influenza A[J];Infection International(Electronic Edition);2012年03期
3 胡瑛;李宝兰;;缺氧诱导因子-1α、2α在恶性肿瘤中不同作用的研究进展[J];癌症进展;2014年02期
4 封少龙;曾灿;杨峗;曹朝晖;;芳香烃受体在肿瘤发生发展过程中的作用[J];癌变.畸变.突变;2014年03期
5 伯铭羽;王向东;张罗;;基质金属蛋白酶及其组织抑制因子在慢性鼻-鼻窦炎中的研究进展[J];中国耳鼻咽喉头颈外科;2014年04期
6 蔡建良;官树雄;麦周生;章诗富;;变应性及非变应性鼻炎患者白细胞介素-16、17的表达及意义[J];广东医学;2014年09期
7 罗晨煜;;我国电子垃圾回收与健康保护机制[J];经营管理者;2014年32期
8 张沈华;申聪香;文忠;李冠雪;杨柯柯;史欣;;Nods样模式识别受体在鼻息肉组织中的表达及意义[J];临床耳鼻咽喉头颈外科杂志;2013年20期
9 Jing Bai;Xiaomin Sun;Chenxi Zhang;Chen Gong;Jingtian Hu;Jianghua Zhang;;Mechanism and kinetics study on the ozonolysis reaction of 2,3,7,8-TCDD in the atmosphere[J];Journal of Environmental Sciences;2014年01期
10 杨敏;韩吉龙;岳耀敬;史兆国;郭婷婷;吴瑜瑜;王朝风;郭健;刘建斌;孙晓萍;牛春娥;杨博辉;;藏羊HIF-1α基因CDS区多态性及生物信息学分析[J];江苏农业科学;2013年10期
相关会议论文 前1条
1 程晓蕾;陈宏;;Th17细胞与变态反应性疾病的研究现状[A];第六次全国中西医结合变态反应学术大会论文汇编[C];2013年
相关博士学位论文 前10条
1 吴俊华;鼻息肉组织中BMP信号活性及E-cadherin表达失调与疾病进展的相关性研究[D];华中科技大学;2010年
2 刘火旺;复发性鼻息肉分子标志物筛选及其意义[D];中南大学;2010年
3 付志婕;经典型瞬时感受器电位通道在鼻息肉中的作用及机制研究[D];山东大学;2013年
4 李旭;ROS依赖的内质网应激—自噬反应在醉茄素A诱导人胰腺癌细胞凋亡中的作用研究[D];华中科技大学;2013年
5 胡双;克拉霉素和地塞米松在不同类型CRS中作用的初步探讨[D];华中科技大学;2013年
6 袁立来;典型多环芳烃暴露对稀有泩鲫药物代谢系统相关基因表达的影响[D];华中农业大学;2013年
7 敬晓棋;乳腺炎细胞因子及T淋巴细胞亚群研究[D];西北农林科技大学;2013年
8 寇巍;鼻息肉患者Treg/Th17细胞表达与TGF-β1相关性及鼻用激素干预的研究[D];重庆医科大学;2013年
9 王晓强;STAT3信号通路在鼻息肉发病机制中作用的初步研究[D];重庆医科大学;2013年
10 罗启慧;肺炎链球菌感染猕猴肠道菌群分子解析及消化、呼吸、免疫系统免疫相关因子的表达[D];四川农业大学;2012年
相关硕士学位论文 前10条
1 阮丽君;RVVC证候特点与患者阴道局部IL-4、IL-12、IFN-γ水平的研究[D];广州中医药大学;2012年
2 赵淑敏;山东地区慢性鼻—鼻窦炎患者诊疗认识度的问卷调查[D];山东大学;2013年
3 齐莹;基于离子液体/纳米材料复合的电化学传感器在环境激素分析中的应用[D];湘潭大学;2012年
4 钱亚f;中鼻甲泡与鼻中隔偏曲及两者与慢性鼻—鼻窦炎关系[D];浙江大学;2012年
5 房光萃;自身免疫性心肌炎中Th17/Treg细胞的变化与意义[D];福建医科大学;2013年
6 石小伟;晋西北某地变应性鼻炎的发病特点及Th17、CD4~+CD25~+Foxp3~+调节性T细胞在外周血中的表达[D];安徽医科大学;2013年
7 余茜;芳香烃受体及相关基因在人皮脂腺细胞上表达及其意义的研究[D];安徽医科大学;2013年
8 黄方杰;重症肌无力发病机制以及相关自身抗体研究[D];天津医科大学;2013年
9 于小璇;Th17、Treg细胞以及相关细胞因子与寻常型天疱疮发病相关性的研究[D];昆明医科大学;2013年
10 高辰;指示非二VA英类多氯联苯和植物生长素的新型报告体系的构建[D];浙江大学;2013年
本文编号：2192928
本文链接：https://www.wllwen.com/yixuelunwen/yank/2192928.html
最近更新
教材专著
