LncRNA GAS5 inhibits Th17 differentiation and alleviates immune thrombocytopenia via promoting the ubiquitination of STAT3

BackgroundThe increased differentiation of T helper 17 cells (Th17) accelerates the development of immune thrombocytopenia (ITP), which is a common autoimmune disease with limited therapeutic methods. Recent studies have revealed that long non-coding RNAs (lncRNAs) play a critical role in autoimmune diseases, thus this study aims to investigate the effect of lncRNA GAS5 on the differentiation of Th17 cells in ITP.MethodsThe expression of GAS5 in peripheral blood mononuclear cells (PBMCs) of ITP patients and spleen tissues of ITP mice was measured by qRT-PCR. The percentage of Th17 cells in CD4⁺ cells was measured by flow cytometry. The combination between GAS5 and STAT3 was confirmed by RNA pull-down assay and RNA Binding Protein Immunoprecipitation (RIP). The ubiquitination of STAT3 was detected by ubiquitination assay and the interaction between STAT3 and TRAF6 was measured by Co-Immunoprecipitation (Co-IP). Finally, the effect of GAS5 on Th17 differentiation was investigated in vitro and in vivo using lentivirus (lenti)-GAS5.ResultsGAS5 expression was downregulated both in PBMCs of ITP patients and spleen tissues of ITP mice. Overexpression of GAS5 suppressed Th17 differentiation while had no effect on Treg differentiation in naïve CD4⁺ cells. RNA pull-down and RNA immunoprecipitation assays confirmed the interaction between GAS5 and STAT3. Further studies showed GAS5 accelerated the degradation of STAT3 via promoting TRAF6-mediated ubiquitination. Overexpressing GAS5 suppressed Th17 differentiation in vitro and alleviated ITP in vivo via reducing STAT3.ConclusionLncRNA GAS5 inhibited Th17 differentiation through promoting the TRAF6-mediated ubiquitination of STAT3, thus relieving ITP.     

Increased IL-10/IL-17 ratio is aggravated along with the prognosis of patients with chronic lymphocytic leukemia

ObjectiveThis study is to investigate the association between the Treg/Th17 cells and prognosis of chronic lymphocytic leukemia (CLL).MethodsTotally 50 CLL patients and 20 Health controls were included in this study. Regulatory T (Treg) cells and the cell subset secreting IL-17 (Th17) in peripheral blood were detected with flow cytometry. Serum levels of IL-10 and IL-17 were determined with ELISA, and expression of Foxp3 and RORγt was assessed with quantitative real-time PCR.ResultsTreg and Th17 cell proportions in peripheral blood in the CLL patients were significantly higher than control. Serum levels of IL-10 and IL-17, and expression of Foxp3 and RORγt, were significantly increased in the CLL patients. Ratios of Treg/Th17 and IL-10/IL-17 were significantly elevated in the CLL patients. Compared with those before treatment, Treg/Th17 and IL-10/IL-17 ratios were declined in the CLL patients in remission. Compared with the non-remission group, Treg cells were significantly decreased, while Th17 cells were significantly increased, resulting in decreased Treg/Th17 ratio, in the remission group. Moreover, the serum IL-10 level was significantly decreased, while the serum IL-17 level was significantly increased, resulting in declined IL-10/IL-17 ratio, in the remission group. Correlation analysis showed that, Treg and Th17 cell counts were significantly associated with CD38 and ZAP-70 expression in the CLL patients. Moreover, the IL-10/IL-17 ratio was also significantly associated with CLL prognostic factors.ConclusionAltered Treg/Th17 and IL-10/IL-17 ratios in CLL would be aggravated along with the disease progression, which might be used as indicators for the disease prognosis.     

IL-17 targeted therapies for psoriasis

Introduction: Psoriasis is a chronic, disabling, inflammatory skin disease whose pathogenesis still remains to be fully elucidated. Genetic and environmental factors induce an immune response mediated by several cytokines and chemokines, including IL-17A.

Areas covered: Emerging evidence now suggests that IL-17A is central in the pathogenesis of psoriasis. Three agents neutralizing IL-17 (i.e., secukinumab and ixekizumab) or antagonizing its receptor (i.e., brodalumab) are in development and are being studied in Phase III clinical trials to evaluate their overall efficacy and safety. However, Phase II results of IL-17 blockade with each of these agents has shown a marked improvement of disease severity, thus confirming the pathogenic relevance of IL-17 in mediating crucial inflammatory circuits in psoriasis.

Expert opinion: Anti-IL-17 agents are likely to become important future therapeutics in this disease and the may potentially impact on cardiovascular diseases, arthritis and other comorbidities associated with psoriasis.     

sST2/IL-33与Th17/Treg相关细胞因子在原发免疫性血小板减少症中的作用研究

目的 观察可溶性ST2（sST2）和白细胞介素（IL）-33在原发免疫性血小板减少症（ITP）中的表达水平变化及其对Th17/Treg细胞平衡的调节机制。方法 30例ITP患者作为ITP组,选取同期健康体检者20例作为对照组,采用酶联免疫吸附试验（ELISA）检测 2组外周血血清中 IL-33、sST-2、IL-17和转化生长因子-β（TGF-β）的水平。结果 与对照组比较,ITP组血清sST2及IL-17水平均升高（P＜0.01）,TGF-β表达水平降低（P＜0.01）,而IL-33的表达水平差异无统计学意义（P＞0.05）;在 ITP 组中 sST2 与 TGF-β 呈负相关（r=-0.471,P＜0.01）,与 IL-17 无相关性（r=0.189,P＞0.05）。结论 sST2表达水平增加和Th17/Treg细胞失衡可能是导致ITP发病的免疫机制之一。     

Anti-interleukin-17 antibodies attenuate airway inflammation in tobacco-smoke-exposed mice

Context: Our previous study showed that the interleukin-17 (IL-17) concentration in lung tissue and in bronchoalveolar lavage fluid (BALF) of rats with tobacco-smoke-induced chronic obstructive pulmonary disease (COPD) was higher than that of control group. However, whether IL-17 inhibitor could decrease the effect of tobacco smoking is not known yet.

Objectives: To investigate the significance of IL-17 antibodies (Ab) in tobacco-smoke-exposed (TSE) mice.

Materials and methods: Male C57/BL6 mice were randomly divided into three groups: TSE group, TSE + anti-IL-17 Ab group, and control group. The number of cells in BALF and the concentrations of IL-17, IL-6, IL-8 and MUC5AC in BALF and lung tissue homogenate were measured. Pulmonary function was measured by pressure sensors, and histologic analysis of the lungs was done in each group.

Results: Lung function tests in TSE + anti-IL-17 Ab group were the same compared with TSE group (P?>?0.05). The total cell count and the number of neutrophil cells in BALF were significantly higher in TSE group than the normal control group (P?<?0.01). Compared with the TSE group, the total cell count in TSE + anti-IL-17 Ab group was decreased, and the percentage of neutrophils in BALF was highly decreased (P?<?0.01). Airway inflammation was alleviated in TSE + anti-IL-17 Ab group by histologic analysis. The concentrations of IL-17 in lung tissue were significantly lower in TSE + anti-IL-17 Ab group than in TSE group (P?<?0.01). IL-17 was mainly expressed in the epithelial cells in the airways of TSE mice. The concentration of IL-6, IL-8 and MUC5AC in BALF was decreased in TSE + anti-IL-17 Ab group compared with TSE group.

Discussion and conclusions: These data support a potential role for IL-17 in airway neutrophilic inflammation in TSE mice. Anti-IL-17 decreased the number of neutrophils as well as the concentration of MUC5AC in the BALF and attenuated neutrophilic airway inflammation.     

CNI induced Th17/Treg imbalance and susceptibility to renal dysfunction in renal transplantation

Calcineurin inhibitors (CNI) prevent graft rejection by blocking interleukin-2 (IL-2), which was required for development and function of Foxp3⁺CD4⁺CD25⁺ regulatory T cells (Treg). Recently, IL-2 was reported to play a part in the inhibition of Th17 cells. The renal transplantation recipient who used CNI regularly might have Th17/Treg imbalance with increased Th17 cells and decreased Treg cells, which would cause renal dysfunction even rejection. To assess the effect of CNI on Th17 cells and Treg cells, we included 123 renal transplantation recipients (101 in a stable stage and 22 with renal dysfunction) and 27 healthy volunteers. Among all the recipients, 103 recipients used CNI and 20 recipients used sirolimus without CNI. The recipients who used CNI were further classified into four groups according to the blood levels of CNI: Of all these subjects, Th17 and Treg frequencies in the peripheral blood were analyzed by flow cytometry (FCM). Serums IL-17, IL-23, IL-6, IFN-r, and TGF-β were analyzed by ELISA. The results demonstrated that the transplantation recipient treated by CNI revealed an obvious increase in peripheral Th17 frequencies and a significant decrease in Treg frequencies when compared with the sirolimus group and healthy people (P < 0.05). Even more, the transplantation recipient with renal dysfunction had the highest level of Th17 cells (P < 0.05) while the lowest Treg cells compared with stable recipient and healthy control, with increased serums IL-6 and IL-17. Our results indicated that CNI was associated with Th17/Treg imbalance in peripheral blood, which supported the followed generation of renal dysfunction after transplantation.     

玉屏风颗粒联合双嘧达莫治疗儿童过敏性紫癜的临床研究

目的 探讨玉屏风颗粒联合双嘧达莫片治疗儿童过敏性紫癜的临床疗效。方法 选取2020年1月-2022年10月在皖西卫生职业学院附属医院就诊的85例过敏性紫癜患儿,按照计算机随机排列法分为对照组(42例)和治疗组(43例)。对照组口服双嘧达莫片,3.0 mg/(kg·d),平均分3次服用。治疗组在对照组基础上温水冲服玉屏风颗粒,3~8岁,3次/d,半袋/次,8~12岁,3次/d,1袋/次。两组患儿连续治疗3个月。观察两组临床疗效,比较两组的主要症状消失时间、可溶性髓样细胞表达触发受体样转录因子1(TLT1)、白细胞介素(IL)-9、IL-21、辅助性T细胞(Th17)、调节性T细胞(Treg)、Th17/Treg水平。结果 治疗后,治疗组的总有效率95.35%较对照组的80.95%更高(P<0.05)。治疗后,治疗组患儿皮肤紫癫、腹痛、关节症状、肾脏症状消失时间均短于对照组(P<0.05)。治疗后,两组的血清TLT1、IL-9水平明显降低,血清IL-21水平明显升高(P<0.05);治疗后,治疗组的血清TLT1、IL-9水平低于对照组,血清IL-21水平高于对照组(P<0.05)。治疗后,两组的Th17、Th17/Treg水平低于治疗前,Treg水平高于治疗前(P<0.05);治疗后,治疗组的Th17、Th17/Treg水平低于对照组,Treg水平高于对照组(P<0.05)。结论 玉屏风颗粒联合双嘧达莫片可用于儿童过敏性紫癜,能够改善临床症状,减轻炎症反应,调节免疫功能平衡,且药物安全性良好。     

LncRNA XLOC_003810 modulates thymic Th17/Treg balance in myasthenia gravis with thymoma

Imbalance of T helper 17 (Th17)/regulatory T (Treg) cells is involved in the pathogenesis of myasthenia gravis with thymoma (MG-T). Long non-coding RNAs (lncRNAs) are implicated in the regulation of Th17/Treg balance. This study was designed to explore the role of XLOC_003810, a novel lncRNA, in regulating the Th17/Treg balance in MG-T. The thymic CD4⁺ T cells were isolated from control subjects and MG-T patients. The Th17/Treg balance was evaluated by determining proportions of Th17 and Treg cells and expression of Th17- and Treg- associated molecules. Lentivirus-mediated silencing and overexpression of XLOC_003810 in CD4⁺ T cells were performed. The results showed that XLOC_003810 expression was higher in MG-T thymic CD4⁺ T cells than that in the control group. Furthermore, the ratio of Th17/Treg cells, proportion of Th17 cells and levels of Th17-associated molecules were significantly increased, whereas the proportion of Treg cells and levels of Treg-associated molecules were decreased in MG-T thymic CD4⁺ T cells. Importantly, the Th17/Treg imbalance in MG-T thymic CD4⁺ T cells was aggravated by XLOC_003810 overexpression, whereas it was attenuated by XLOC_003810 silencing. Collectively, XLOC_003810 modulates thymic Th17/Treg balance in MG-T patients, providing the scientific basis for the clinical targeted therapy of MG-T.     

舒芬太尼复合丙泊酚靶控输注对宫颈癌根治术患者Th17/Treg及氧化抗氧化系统的影响

目的 探讨舒芬太尼复合丙泊酚靶控输注对宫颈癌根治术患者T细胞 17(Th17)/调节性 T 细胞(Treg)及氧化抗氧化系统的影响。方法 选取2019年10月-2021 年 10 月延安市人民医院行宫颈癌根治术患者 80 例为研究对象,采用随机数字表法分为对照组和试验组,每组各 40 例,两组患者均行全身麻醉下腹腔镜宫颈癌根治术治疗,术中对照组行芬太尼复合丙泊酚靶控输注;试验组行舒芬太尼复合丙泊酚靶控输注。比较两组麻醉前 1 h、麻醉后 1 h、手术结束后 1 h 血清 Th17/Treg 相关指标(Th17、Treg、Th17/Treg)、氧化抗氧化系统相关指标[超氧化物歧化酶(SOD)、丙二醛(MDA)、过氧化氢酶(CAT)]水平,分别于术毕、术后 6 h、术后 12 h 对两组患者进行疼痛程度评分(VAS 评分)。结果 麻醉后 1 h、手术结束后 1 h 两组血清 Treg 水平均较麻醉前 1 h 显著降低(P<0.05),麻醉后 1 h、手术结束后 1 h 两组血清 Th17、Th17/Treg水平均较麻醉前 1 h 显著升高(P<0.05);试验组麻醉后 1 h、手术结束后 1 h 血清 Treg 水平高于对照组,Th17、Th17/Treg水平低于对照组(P<0.05);麻醉后 1 h、手术结束后 1 h 两组 SOD、CAT、MDA 水平均较麻醉前 1 h 升高,差异有统计学意义(P<0.05);试验组麻醉后 1 h、手术结束后 1 h 血清 SOD、CAT 水平高于对照组,MDA 水平低于对照组(P<0.05);试验组术后 6、12 h VAS 评分均显著低于对照组(P<0.05)。结论 与芬太尼复合丙泊酚靶控输注比较,宫颈癌患者根治术中采用舒芬太尼复合丙泊酚靶控输注能降低手术及麻醉对患者 Th17/Treg 及氧化抗氧化系统的影响,改善镇痛效果。     

Human adipose tissue-derived mesenchymal stem cells in rheumatoid arthritis: Regulatory effects on peripheral blood mononuclear cells activation

Background and objectivesMesenchymal stem cells (MSCs) are multipotent adult stem cells with immunomodulatory properties. The mechanisms by which MSCs inhibit the proliferation of pro-inflammatory T cells have not been fully elucidated yet. It is assumed that pro-inflammatory T-cells play an important role in the development of autoimmune diseases. We investigated the potential therapeutic effects of human adipose tissue derived (Ad)-MSCs on the peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA) patients and healthy individuals, with a particular focus on Th17-associated cytokines.Materials and methodsPBMCs from RA patients and healthy donors were co-cultured with Ad-MSCs and HeLa with or without Phytohemagglutinin (PHA). Finally, IL-6, IL-17, IL-21, IL-23 and TGF-β levels were determined by ELISA and quantitative real-time RT-PCR on co-culture supernatants and PBMCs, respectively.ResultsIn co-culture interaction, Ad-MSCs inhibited IL-17 secretion by PBMCs compared to unstimulated PBMCs cultured alone. In addition, IL-21 expressions in PBMCs of the patient group, and IL-17 and IL-21 in healthy group were inhibited by Ad-MSCs compared to PBMCs cultured alone. TGF-β expression in healthy individuals remarkably increased in both MSC-treated groups with and without PHA in comparison to PHA-stimulated and -unstimulated PBMCs.ConclusionsThis study demonstrates that human Ad-MSCs act as key regulators of immune tolerance by inhibiting the inflammation. Therefore, they can be attractive candidates for immunomodulatory cell-based therapy in RA.     

结核患者外周血中辅助性T细胞17及白细胞介素-17水平的变化

目的:探讨结核患者外周血辅助性T细胞17(Th17细胞)及白细胞介素-17(IL-17)水平变化及意义。方法:以结核患者98例(初治58例,复治40例)、健康对照者98例为研究对象,抽取研究对象外周血并分离外周血单核细胞(PBMC)和血浆,采用流式细胞术(FCM)检测PBMC中Th17细胞的百分率,酶联免疫吸试验(ELISA)检测血浆中IL-17水平;用灭活的结核分枝杆菌菌株(H37Rv)分别刺激结核患者和健康对照者PBMC,ELISA法检测其上清中IL-17水平。结果:与健康对照者比较,结核患者外周血Th17细胞比例[(5.2±1.8)%vs(1.8±1.4)%,P<0.05]及IL-17水平[(68.22±10.31)vs(39.81±14.58)pg/ml,P<0.01]显著增高;与初治组比较,复治组Th17细胞比例[(6.4±1.8)%vs(3.8±1.3)%,P<0.05]及IL-17水平[(85.46±9.13)vs(51.22±12.36)pg/ml,P<0.05]显著增高;结核患者血浆IL-17水平与Th17细胞的比例呈正相关(r=0.912,P<0.05);H37RV刺激结核病人和健康对照者PBMC后上清中均有IL-17的表达,且结核病人来源的表达水平更高。结论:结核患者外周血Th17细胞比例及IL-17水平增高,Th17细胞和IL-17在结核病的发生发展中发挥了重要作用。     

Are Th17 cells and their cytokines a therapeutic target in Guillain–Barré syndrome?

Introduction: Guillain–Barré syndrome (GBS) is an immune-mediated inflammatory disorder of the peripheral nervous system (PNS). Experimental autoimmune neuritis (EAN) is a useful animal model for studying GBS. Currently, GBS remains a life-threatening disorder and more effective therapeutic strategies are in urgent need.

Areas covered: Accumulating evidence has revealed that T helper (Th) 17 cells and their cytokines are pathogenic in GBS/EAN. Drugs attenuated clinical signs of GBS/EAN, in part, by decreasing Th17 cells or IL-17A. Th17 cells and their cytokines might be potential therapeutic targets. Approaches targeting Th17 cells or their cytokines are in development in treating Th17 cells-involved disorders. In this review, we summarize the up-to-date knowledge on roles of Th17 cells and their cytokines in GBS/EAN, as well potential approaches targeting Th17 cells and their cytokines as clinical applications.

Expert opinion: As Th17 cells produce different sets of pro-inflammatory cytokines and Th17-related cytokines are not exclusively produced by Th17 cells, targeting Th17 cell development may be superior to blocking a single Th17 cytokine to treat Th17 cells-involved disorders. Considering the essential role of retinoic acid-related orphan receptor γT (RORγT) and IL-23 in Th17 cell development, RORγT inhibitors or IL-23 antagonists may provide better clinical efficacy in treating GBS/EAN.     

Real-world incidence of inflammatory bowel disease among patients with other chronic inflammatory diseases treated with interleukin-17a or phosphodiesterase 4 inhibitors

Objectives: (1) To assess the real-world incidence of inflammatory bowel disease (IBD) in patients with or without other chronic inflammatory diseases (CIDs), and (2) to understand whether IBD incidence differs in CID patients receiving interleukin-17a signaling antagonists (anti-IL-17a) or phosphodiesterase 4 inhibitors (PDE4i) versus patients using a biologic not indicated for IBD or biologic-naïve patients.

Methods: The MarketScan Research Databases (January 2010–July 2017) were used. A CID population was created from patients with ankylosing spondylitis, psoriatic arthritis, psoriasis or rheumatoid arthritis (RA). The CID population was stratified into different cohorts based on the baseline treatments received: (1) anti-IL-17a, (2) PDE4i, (3) biologic-naïve, and (4) non-IBD-indicated biologic (i.e. biologics not indicated for the treatment of IBD and excluding anti-IL-17a and PDE4i); a non-CID cohort was also created. The 1?year incidence rate (IR) of IBD was compared between cohorts using a logistic regression model adjusting for baseline characteristics.

Results: CID cohorts included older patients than the non-CID cohort (mean age range: 48.4–54.4 versus 46.3?years). The 1?year IR of IBD was 1.41% in the anti-IL-17a cohort (N?=?355), 0.68% in the PDE4i cohort (N?=?2195), 0.47% in the biologic-naïve cohort (N?=?424,767), 0.51% in the non-IBD-indicated biologic cohort (N?=?56,317) cohort and 0.25% in the non-CID cohort (N?=?1,008,436). After 1?year of follow-up, the odds of having IBD were 2.85 (p?=?.0213) and 1.42 (p?=?.1891) times higher in the anti-IL-17a and PDE4i cohorts, respectively, compared to the biologic-naïve cohort, and 2.86 (p?=?.0253) and 1.21 (p?=?.4978) times higher compared to the non-IBD-indicated biologic cohort. Similar results were observed in sensitivity analyses where patients with RA only were excluded (since anti-IL-17a and PDE4i agents are not indicated for RA).

Conclusions: Anti-IL-17a treatment was associated with a nearly three-fold higher risk of IBD in CID patients. Treatment decisions for patients with CIDs should take into account the risk of developing of IBD.     

Regulatory effect of daphnetin, a coumarin extracted from Daphne odora, on the balance of Treg and Th17 in collagen-induced arthritis

Daphnetin extracted from Daphne odora Var. marginata contains coumarin compounds, which possess properties of analgesic and anti-inflammatory effects. In this study, we investigated the therapeutic effect of daphnetin on anti-arthritis and its role on the balance of Tregs and Th17, using a collagen-induced arthritis rat model. Collagen-induced arthritis rats were treated with daphnetin for 21 days. The therapeutic effects of daphnetin were evaluated by clinical symptoms and histopathology. The levels of Th17-, Treg-, Th2-, Th1-type cytokines in serum were determined by ELISA. The expression levels of related receptors RORγt, NF-κB, Foxp3 and CD77 in joint tissues were detected by immunohistochemistry. Our results showed that administration of daphnetin significantly alleviated the severity of the arthritis, as evidenced by the reduction of arthritis scores, suppression of the infiltration of inflammatory cells and prevention of synovial hyperplasia, thereby resulting in the joint destruction in the arthritis rats. Additionally, daphnetin treatment reduced the serum level of Th17-, Th2- and Th1-type in collagen-induced arthritis rats. Correspondingly, the expression of RORγt, NF-κB and CD77 in joint tissue of collagen-induced arthritis rats was remarkably decreased, while the expression of Foxp3 and IL-10 was remarkably increased after being administered with daphnetin. Collectively, this study demonstrated that administration of daphnetin attenuated the clinical symptoms and pathological destruction of arthritis joints. The therapeutic effects were associated with the up-regulation of Tregs, down-regulation of Th17-, Th2- and Th1-type cell responses. The results provide novel evidence that daphnetin has therapeutic effects on autoimmune arthritis through modulating the balance of Tregs and Th17.     

Thymol as a reciprocal regulator of T cell differentiation: Promotion of regulatory T cells and suppression of Th1/Th17 cells

Regulatory T cells (Tregs) are critical for maintaining immune response and enhancing their differentiation has therapeutic implications for autoimmune diseases. In this study, we investigated the effects of thymol a well-known monoterpene from Thyme on differentiation and function of Tregs. In vitro generation of Tregs from purified naïve CD4⁺CD25⁻ T cells in the presence of thymol was carried out. Suppressor activity of generated Tregs was examined by changes in the proliferation of CFSE-labeled conventional T cells. Thymol promotes differentiation of naïve CD4⁺CD25⁻ T cells to CD4⁺CD25⁺Foxp3⁺ Tregs [66.9–71.8% vs. control (47%)] and increased intensity of Foxp3 expression on Tregs (p < 0.01). In functional assay, an increased immune suppression by thymol-induced Tregs (≈2.5 times of untreated Tregs) was detected. For in vivo study, thymol was intraperitoneally administered to ovalbumin (Ova)-immunized mice. Flow cytometry assessment of spleens from thymol-treated Ova-immunized mice showed increased number of CD4⁺ Foxp3⁺ Tregs (>8%, p < 0.01(and decreased levels of CD4⁺T-bet⁺ Th1 and CD4⁺RORγt⁺ Th17 cells resulted in significant decreased Th1/Treg and Th17/Treg ratios. In ex vivo Ova challenge of splenocytes from thymol-treated Ova-immunized mice, similarly higher levels of CD4⁺ Foxp3⁺ Tregs, and also elevated TGF-β expression in CD4⁺Foxp3⁺ population (48.1% vs. 18.9% in untreated Ova-immunized group) and reduced IFN-γ-producing CD4⁺T-bet⁺ T cells and IL-17-producing CD4⁺RORγt⁺ T cells were detected. This led to marked decreased ratios of IFNγ/TGF-β and IL-17/TGF-β expressions. In conclusion, this study revealed thymol as a compound with enhancing effects on Treg differentiation and function, which may have potential benefits in treatment of immune-mediated diseases with Th1/Th17 over-activation.     

Allergen induced Th17 response in the peripheral blood mononuclear cells (PBMCs) of patients with nasal polyposis

BackgroundNasal polyposis (NP) is a chronic inflammatory disease of the nasal cavity and sinuses. Th17 cells have been considered to play roles in allergic airway diseases and various chronic inflammatory disorders.Aim of the studyThis study aimed to investigate the population and function of peripheral Th17 cells in response to house dust mite extracts (HDM) allergen in NP patients, and evaluate the possible correlation between Th17 cells and atopy, to explore the role of atopy in the pathogenesis of NP.MethodsPeripheral blood mononuclear cells (PBMCs) obtained from atopic NP patients, non-atopic NP patients, and controls were stimulated by phytohemagglutinin (PHA) or HDM plus PHA. The resulting frequency of Th17 cells was detected by flow cytometry and the expression of RORc was measured by real-time PCR. Then the concentrations of IL-17A, INF-γ, IL-4 and IL-5 in the supernatants were assayed by specific ELISAs.ResultsThe population and function of Th17 cells in allergen stimulated PBMCs were significantly higher in atopic NP patients. In addition, in atopic group, HDM + PHA stimulation induced significant increase of Th17 population and IL-17A production versus those in PHA stimulated ones. However, the frequency of Th17 cells was not correlated with Th1, Th2 cytokine productions.ConclusionTh17 immunity is involved in the systemic immune responses to allergen in atopic NP and atopy may aggravate NP by stimulating the increase of Th17 population and IL-17A production. The mechanism of Th17 cells response to allergen may be regulated differently from the regulation of Th1 and Th2 immunity in NP.