Inverse modulation of IL-10 and IL-12 in the blood of women with preneoplastic lesions of the uterine cervix

It has been postulated that an impaired immune response may contribute to the progression of human papillomavirus (HPV)-associated preneoplastic lesions. Based on this hypothesis, we evaluated the cytokine production in the blood of patients with squamous intraepithelial lesions (SIL) of the uterine cervix. The levels of type-1 (interferon-gamma (IFN-γ) and IL-12) and type-2 (IL-4 and IL-10) cytokines were measured in whole blood culture supernatants of patients with low- and high-grade SIL and control women. There was no difference in IL-4 and IFN-γ levels between patients with SIL and the control group. In contrast, the ratio of IL-12/IL-10 levels was significantly lower in patients with SIL compared with the control group. A lower IL-12/IL-10 ratio in women with SIL was also observed when peripheral blood mononuclear cell (PBMC) culture supernatants and plasma samples were analysed. In patients, neither the lower expression of the CD3ε chain nor the higher frequency of HLA-DRB1*1501 expression could be correlated with abnormal cytokine production. These results suggest that a part of the cytokine network, namely IL-10 and IL-12, is perturbed in patients with SIL. A better knowledge of the role of these cytokines in regulating the growth of HPV-associated SIL might have practical implications for the development of vaccines or immunomodulatory strategies in the treatment of cervical cancers.     

肝硬化患者血清TGF-β1、IL-10、IL-12和IL-18检测的应用价值

目的：详述肝硬化患者血清TGF-β1、IL-10、IL-12和IL-18水平的变化及临床意义。方法：应用酶联法对66例肝硬化患者（其中30例为肝硬化腹腔积液组,36例为肝硬化无腹腔积液组）进行了血清TGF-β1、IL-10、IL-12和IL-18测定并与35例正常人作比较。结果：肝硬化患者血清TGF-β1、IL-10、IL-12和IL-18水平均非常显著地高于正常人组（P〈0.01）,尤以肝硬化腹腔积液组为甚。肝硬化患者血清TGF-β1水平与IL-10、IL-12和IL-18水平呈正相关（r=0.5018、0.5742、0.6011,P〈0.01）。结论：检测肝硬化患者血清TGF-β1、IL-10、IL-12和IL-18水平的变化有助于对疾病变化过程和治疗功效的评估,因而可提供重要的临床价值。     

Regulation of interleukin-12 receptor β1 chain expression and interleukin-12 binding by human peripheral blood mononuclear cells

The interleukin-12 receptor (IL-12R)β1 chain is an essential component of the functional IL-12R on both human T and natural killer cells. In this report it is shown that activation of human peripheral blood mononuclear cells (PBMC) with anti-CD3 monoclonal antibody (mAb) or phytohemagglutinin resulted in the up-regulation of IL-12Rβ1 expression and IL-12 binding. Kinetic studies revealed that maximum expression of IL-12Rβ1 and IL-12 binding occurred on days 3–4. Anti-CD3-induced expression of IL-12Rβ1 chain and IL-12 binding by PBMC was augmented by anti-CD28 mAb, indicating that the potentiating effect of anti-CD28 on T cell responses to IL-12 could be mediated, at least in part, by the enhancement of IL-12R expression. Among 16 cytokines tested, IL-2, IL-7 and IL-15 markedly induced IL-12Rβ1 expression and IL-12 binding on resting PBMC, whereas IL-1α and tumor necrosis factor-α had a minimal enhancing effect. In contrast, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, interferon (IFN)-α, IFN-γ, granulocyte/macrophage colony-stimulating factor and transforming growth factor (TGF)-β2 had no detectable enhancing effect. Anti-CD3-induced expression of IL-12Rβ1 and of low-affinity IL-12 binding sites was partially inhibited by TGF-β2, IL-10 and IL-4; however, TGF-β2 and IL-10 completely abolished anti-CD3-induced expression of high-affinity IL-12 binding sites. Consistent with the reduction of high affinity IL-12 binding sites, PBMC activated with anti-CD3 mAb in the presence of TGF-β2 or IL-10 failed to produce IFN-γ or to proliferate in response to IL-12. These results suggest that Th2 cell-derived cytokines can inhibit IL-12-induced biological functions by inhibiting IL-12R expression and that expression of a second subunit of the IL-12R (IL-12Rβ2), required for the formation of high-affinity IL-12 binding sites, may be more highly regulated by TGF-β2 and IL-10 than is expression of IL-12Rβ1.     

Serum levels of TGFβ, IL-10, IL-17, and IL-23 cytokines in β-thalassemia major patients: the impact of silymarin therapy

Several immunological abnormalities have been characterized in β-thalassemia, many of which are linked to or identified with cytokines. In this study, we investigated the serum levels of TGF-β, IL-10, IL-17 and IL-23 in β-thalassemia major patients in comparison with healthy controls. The immunomodulatory effect of silymarin (a flavonoid complex obtained from Silybum marinum) on the serum levels of cytokines was further evaluated in thalassemia patients receiving silymarin (420?mg/day) and compared with patients treated with placebo for 6-month. Serum cytokines levels were measured by enzyme linked immunosorbent assay (ELISA). The results showed a significant higher concentration of TGF-β and IL-23 in the patient group than control group. Among studied cytokines, a significant reduction in serum IL-10 levels was found in patients treated with silymarin when compared with IL-10 values at baseline. However, no significant difference was observed between baseline values of cytokine compared with end values in placebo group. Our data suggest the presence of imbalanced immune condition involving inflammation and immunosuppression in thalassemia patients, which could be modulated to a more effective immune response by silymarin.     

JAK/STAT信号途径参与高糖诱导的肾小管上皮细胞转分化

目的：观察Janus激酶/信号转导和转录活化因子(JAK/STAT) 信号的激活对高糖诱导肾小管上皮细胞转分化的影响。方法:体外培养人肾近曲小管上皮细胞株（HKCs）,分别给予高糖和JAK拮抗剂AG490干预,采用免疫沉淀和Western印迹检测JAK2的磷酸化;Western印迹检测平滑肌肌动蛋白(α-SMA)、E-钙黏素(E-cadherin)及信号蛋白STAT1、STAT3、磷酸化STAT1 (phospho-STAT1, p-STAT1) 和p-STAT3的水平; 酶联免疫吸附法(ELISA)测定细胞上清液中转化生长因子β₁(TGF-β₁)和I型胶原的分泌,逆转录聚合酶链反应(RT-PCR)检测TGF-β₁mRNA表达。结果:与低糖对照组比较,高糖培养的HKCs中α-SMA 的水平及p-JAK2 、p-STAT1 和p-STAT3 比例明显上调；E-cadherin表达明显下调；TGF-β₁ mRNA 表达增加；细胞培养上清液中TGF-β₁、Ⅰ型胶原分泌增加。AG490明显抑制JAK2磷酸化、下调p－STAT1 和p-STAT3的同时,明显抑制高糖刺激HKCs中α-SMA表达的升高，减轻E-cadherin表达下降程度；降低TGF-β₁ mRNA 表达及TGF-β₁、Ⅰ型胶原的分泌。结论:JAK/STAT信号途径参与高糖诱导的HKCs转分化，并刺激TGF-β₁和细胞外基质的分泌。     

Local cytokine profiles of patients with cervical intraepithelial and invasive neoplasia

Several studies have suggested that patients with cervical intraepithelial and invasive neoplasia have reduced levels of Th1 cytokines, and increased levels of Th2 cytokines. Thus, the aim of this study was to delineate the immunological profile associated with lesion progression. Biopsies were obtained from 28 patients with low grade cervical intraepithelial lesions (LSILs), 53 patients with high grade cervical intraepithelial lesions (HSILs), 25 patients with invasive cancer (CA), and 20 healthy controls. Levels of IFN-γ, TNF-α, IL-2, IL-4, IL-10, IL-12, TGF-β1 and TGF-β2 were then assayed by RT-PCR and ELISA for each biopsy sample. For LSILs, higher levels of Th1 cytokines were detected, while HSILs were associated with a Th2 cytokine profile. In contrast, CA tissues were associated with the strongest expression of a Treg cytokine profile. In conclusion the most important contribution of these work is identification of the Treg cytokine profile in HPV progression lesions and in combination, these results suggested that tumor progression is dependent on suppression of cellular immunity.     

The complex alteration in the network of IL-17-type cytokines in patients with hereditary angioedema

Hereditary angioedema (HAE) is a rare autosomic-dominant disorder characterized by a deficiency of C1 esterase inhibitor which causes episodic swellings of subcutaneous tissues, bowel walls and upper airways that are disabling and potentially life-threatening. We evaluated n?=?17 patients with confirmed HAE diagnosis during attack and remission state and n?=?19 healthy subjects. The samples were tested for a panel of IL (Interleukin)-17-type cytokines (IL-1β, IL-6, IL-10, granulocyte–macrophage colony stimulating factor (GM-CSF), IL-17, IL-21, IL-22, IL-23) and transforming growth factor-beta (TGF-β) subtypes. Data indicate that there are variations of cytokine levels in HAE subjects comparing the condition during the crisis respect to the value in the remission phase, in particular type 17 signature cytokines are increased, whereas IL-23 is unmodified and TGF-β3 is significantly reduced. When comparing healthy and HAE subjects in the remission state, we found a significant difference for IL-17, GM-CSF, IL-21, TGF-β1 and TGF-β2 cytokines. These results confirm and extend our previous findings indicating that in HAE there is operating an inflammatory activation process, which involves also T helper 17 (Th17) cytokines and TGF-β isoforms, associated with localized angioedema attacks and characterized by elevated bradykinin levels.     

The group 2 innate lymphoid cell (ILC2) regulatory network and its underlying mechanisms

Group 2 innate lymphoid cells (ILC2s) play critical roles in the induction of type 2 inflammation, response to parasite infection, metabolic homeostasis, and tissue repair. These multifunctional roles of ILC2s are tightly controlled by complex regulatory systems in the local microenvironment, the disruption of which may cause various health problems. This review summarizes up-to-date knowledge regarding positive and negative regulators for ILC2s based on their function and signaling pathways, including activating cytokines (IL-33, IL-25; MAPK, NF-κB pathways), co-stimulatory cytokines (IL-2, IL-7, IL-9, TSLP; STAT5, IL-4; STAT6, TNF superfamily; MAPK, NF-κB pathways), suppressive cytokines (type1 IFNs, IFN-γ, IL-27; STAT1, IL-10, TGF-β), transdifferentiation cytokines (IL-12; STAT4, IL-1β, IL-18), lipid mediators (LTC4, LTD4, LTE4, PGD2; Ca²⁺-NFAT pathways, PGE2, PGI2; AC/cAMP/PKA pathways, LXA4, LTB4), neuropeptides (NMU; Ca²⁺-NFAT, MAPK pathways, VIP, CGRP, catecholamine, acetylcholine), sex hormones (androgen, estrogen), nutrients (butyrate; HDAC inhibitors, vitamins), and cell-to-cell interactions (ICOSL-ICOS; STAT5, B7-H6-NKp30, E-cadherin-KLRG1). This comprehensive review affords a better understanding of the regulatory network system for ILC2s, providing impetus to develop new treatment strategies for ILC2-related health problems.     

Correlation of T-helper secretory differentiation and types of antigen-presenting cells in squamous intraepithelial lesions of the uterine cervix

This study addressed the notion that the progression of cervical cancer is associated with a T-helper 2 (TH2) immunodeviation by analysing cytokine expression in 60 cervical biopsy specimens, spanning the spectrum from normal cervical tissue to high-grade squamous intraepithelial lesions (SILs). The biopsies were analysed by immunohistochemistry for the expression of TH1 [interleukin-2 (IL2), interferon gamma (IFNγ)] and of TH2-type cytokines (IL4, IL6). Positive cells were usually observed in the subepithelial connective tissue, where most CD4+ cells were also detected. The density of IL2+ cells was significantly lower in high-grade SILs than in normal tissues taken either from the ectocervix or from the transformation zone. In contrast, significantly higher densities of IL4+ cells and, to a lesser degree, IL6+ cells were found in SIL biopsies compared with histologically normal tissues taken from the adjacent ectocervical region. A significantly higher IL4+/CD4+ cell ratio was also found in high-grade SILs (82 per cent) than in normal cervical biopsies taken from the transformation zone of healthy women showing squamous metaplasia (27 per cent). The elevated density of TH2+ cells in SIL biopsies was associated with both the expression of HLA-DR by keratinocytes and a diminished number of intraepithelial Langerhans' cells (CD1a+). In conclusion, the increased TH2+/CD4+ cell ratio in SIL biopsies suggest the presence, during cervical carcinogenesis, of a TH2 immunodeviation that could participate in the immunoescape of preneoplastic cervical keratinocytes. © 1998 John Wiley & Sons, Ltd.     

Clinical value of serum IL-27 in allergic rhinitis patients and its relationship with Treg associated cytokine levels

Allergic rhinitis (AR) is a nasal allergic disease mainly mediated by IgE, and the immune response is the pathological basis of AR pathogenesis. Regulatory T cells (Treg) has been confirmed to be involved in the occurrence of AR. IL-27 mediates inflammatory responses and allergic symptoms in AR by promoting Tregs and related factors. Our study aimed to explore the correlation between serum interleukin 27 (IL-27) and Treg associated cytokines in the pathogenesis of AR. Based on the inclusion and exclusion criteria, 69 participants with AR and 50 healthy participants were selected. Their IL-27, IL-10, and TGF-β1 levels were estimated by ELISA. Receiver operating characteristics curve (ROC) was performed to demonstrate the diagnostic efficiency of IL-27 in AR. Pearson correlation analysis was used for correlation analysis. IL-27 in AR patients statistically decreased compared to the control group. Consistently, IL-27 were also negatively correlated with the clinical severity of AR patients. Treg related cytokines including IL-10 and TGF-β1 in AR patients was statistically decreased. In addition, the IL-10 and TGF-β1expressions were positively correlated with IL-27 in AR patients. IL-27 was statistically down-regulated in patients with AR, which is related to insufficient Treg function. Restoring the expression of IL-27 may become a novel approach to treat AR.     

IL-17、IL-23、TGF-β和IL-10在乙型肝炎病毒感染中的表达分析

目的探讨乙肝病毒(hepatitis B virus,HBV)感染患者外周血中几种细胞因子在疾病慢性化及疾病进展中的作用。方法分离HBV慢性感染者及健康人外周血,采用酶联免疫吸附法(ELISA法)检测IL-17、IL-23、TGF-β和IL-10的表达及其与乙肝患者肝功能指标及血清中病毒载量的关系。结果乙肝患者血清中IL-17、IL-23和TGF-β与健康对照比较无明显差异,但IL-10显著增加,IL-17、IL-10与转氨酶水平正相关,TGF-β与转氨酶水平负相关,而IL-10与乙肝病毒DNA载量正相关。结论IL-17、IL-10及TGF-β与HBV感染者肝细胞的炎性损伤有关,对于乙肝患者肝纤维化及疾病进展程度具有提示意义,而IL-10具有促炎和耐受的双重作用,可以预测乙肝感染慢性化及病毒持续感染。     

Grass carp TGF-β1 impairs IL-1β signaling in the inflammatory responses: Evidence for the potential of TGF-β1 to antagonize inflammation in fish

In the present study, effects of TGF-β1 on IL-1β signaling during inflammatory response were examined in grass carp. In grass carp head kidney leukocytes (HKLs), LPS significantly induced the mRNA expression of grass carp TGF-β1 (gcTGF-β1) and IL-1β, indicating the involvement of TGF-β1 and IL-1β in inflammatory process. Using anti-IL-1β antibody to neutralize the endogenous IL-1β, we found that stimulation of IL-1β mRNA expression by LPS was independent on IL-1β itself. Interestingly, recombinant gcTGF-β1 (rgcTGF-β1) suppressed basal and LPS-stimulated IL-1β mRNA expression in spite of immunoneutralizing endogenous IL-1β or not. Given that IL-1β receptor signaling molecule and natural IL-1β inhibitors are the important regulators in IL-1β signaling and activity, the effect of LPS on these molecules' expression was determined in HKLs. Results showed that LPS significantly enhanced the mRNA levels of IL-1 receptor type I (IL-1RI) and II (IL-1RII), IL-1R accessory protein (IL-1Racp) and novel IL-1 family member (nIL-1F). Moreover, the induction of IL-1RII, IL-1Racp and nIL-1F by LPS was IL-1β-dependent since IL-1β immunoneutralization abolished these inductions, implying the involvement of IL-1β auto-induction in these effects. Consistently, TGF-β1 could block basal IL-1RI and nIL-1F mRNA expression, and LPS-induced IL-1RI, IL-1Racp and nIL-1F mRNA expression, suggesting these molecules as the regulatory sites for TGF-β1 to modulate IL-1β signaling. Subsequent in vivo studies showed that bacterial challenge significantly up-regulated IL-1β mRNA expression with a rapid and transient pattern and TGF-β1 mRNA expression with a relatively time-delayed kinetics in head kidney. These expression patterns coincide with their pro-inflammatory and anti-inflammatory roles, respectively. As expected, rgcTGF-β1 could suppress bacterial-induced IL-1β mRNA expression, strengthening the anti-inflammatory role of TGF-β1 in vivo. Taken together, these results to our knowledge provide the first evidence for inducible TGF-β1 expression in inflammatory process, as well as the induction of inflammatory stimuli on IL-1β expression and signaling. In turn, TGF-β1 suppressed the proinflammatory process in vitro and in vivo presumably via interfering IL-1β expression and signaling in inflammatory response, highlighting the potential of TGF-β1 in the control of inflammation in fish.     

妊高征肾病患者血浆ET-1和血清TGF-β1、IL-10检测及其临床意义

目的：探讨妊高征肾病患者治疗前后血浆ET-1和血清TGF-β1、IL-10水平的变化及临床意义。方法：应用放射免疫分析和酶联法对32例妊高征肾病患者进行了治疗前后血浆ET-1和血清TGF-β1、IL-10检测,并与35名正常人作比较。结果：妊高征肾病患者在治疗前血浆ET-1和血清TGF-β1、IL-10均非常显著地高于正常人组（P〈0.01）,经治疗2周后则与正常人组比较无显著性差异（P〉0.05）,血浆ET-1和血清TGF-β1、IL-10水平呈正相关（r=0.4812、0.5784,P〈0.01）结论：检测妊高征肾病患者血浆ET-1和血清TGF-β1、IL-10水平的变化,对患者的病情判断、疗效观察具有重要的临床价值。     

Interleukin-35: odd one out or part of the family?

Summary: Advances in cytokine biology have helped us understand the complex communication that takes place between antigen-presenting cells and cells of the adaptive immune system, such as T cells, which collectively mediate an appropriate immune response to a plethora of pathogens while maintaining tolerance to self-antigens. The interleukin-12 (IL-12) cytokine family remains one of the most important and includes IL-12, IL-23, IL-27, and the recently identified IL-35. All four are heterodimeric cytokines, composed of an α chain (p19, p28, or p35) and a β chain (p40 or Ebi3), and signal through unique pairings of five receptor chains (IL-12Rβ1, IL-12Rβ2, IL-23R, gp130, and WSX-1). Despite the interrelationship between the cytokines themselves and their receptors, their source, activity, and kinetics of expression are quite different. Studies using genetically deficient mice have greatly enhanced our understanding of the biology of these cytokines. However, interpretation of these data has been complicated by the recent realization that p40^−/−, p35^−/−, and Ebi3^−/− mice all lack more than one cytokine (IL-12/IL-23, IL-12/IL-35, and IL-27/IL-35, respectively). In this review, we compare and contrast the biology of this expanded IL-12 family and re-evaluate data derived from the analysis of these dual cytokine-deficient mice. We also discuss how the opposing characteristics of the IL-12 family siblings may help to promote a balanced immune response.     

PDGF-BB、IL-13和TGF-β1诱导真皮成纤维细分泌Ⅰ型胶原蛋白的比较

目的用不同浓度的白介素13(IL-13)、转化生长因子β1(TGF-β1)和血小板源性生长因子BB(PDGF-BB)在体外诱导真皮成纤维细胞,以甄选促进诱导Ⅰ型胶原蛋白高分泌的细胞因子。方法选用出生2d的SD大鼠背部皮肤进行真皮成纤维细胞原代培养,采用免疫荧光技术对其进行纯度鉴定。实验分为4组:PDGF-BB(30ng/mL)组、IL-13(100ng/m)组、TGF-β1(10ng/mL)组和不加任何处理因素的阴性对照组,用MTT法、ELISA检测在24h、48h、72h时的真皮成纤维细胞的增殖情况及培养液中Ⅰ型胶原蛋白的浓度。结果原代培养真皮成纤维细胞的纯度达90%以上。PDGF-BB、IL-13、TGF-β1均能促进真皮成纤维细胞增殖和Ⅰ型胶原蛋白分泌,在48h、72h时PDGF-BB组的培养液中Ⅰ型胶原蛋白浓度明显高于IL-13组、TGF-β1组及阴性对照组(P<0.05)。结论浓度为30ng/mL的PDGF-BB促进真皮成纤维细胞增殖和分泌Ⅰ型胶原蛋白的作用更为显著。     

The interleukin-12 family of cytokines: Therapeutic targets for inflammatory disease mediation

The interleukin (IL)-12 family of cytokines, including IL-12 and IL-23, are important mediators of immune-mediated inflammatory diseases such as psoriasis, multiple sclerosis, rheumatoid arthritis, and Crohn's disease. Interleukin-12 and IL-23 are heterodimeric proteins composed of the common subunit IL-12 p40, which interacts with the IL-12Rβ1 receptor, and the cytokine-specific subunits IL-12 p35 and IL-23 p19, respectively. The cytokines are proinflammatory factors linking innate and adaptive immune responses via the induction and differentiation of the T helper cell 1 pathway. Interleukin-12 and IL-23 target different subpopulations of T cells and antigen-presenting cells, as evidenced by their slightly different, but possibly clinically significant, characteristics and functions. Because both share the p40 subunit, the use of anti-IL-12 antibodies may not be as clinically effective as the use of anti-IL-12 p40 antibodies, since both IL-12 and IL-23 share the subunit, which compete, for the IL-12Rβ1 receptor. Also, while IL-12 is a key factor that drives T helper cell 1 responses and interferon-gamma production in the early phases of the immune responses, it may play a relatively minor immunoregulatory role in late-stage inflammation at the point when IL-23 strongly supports the inflammatory process. Thus, direct IL-23 blockade may be key in treating some inflammatory autoimmune diseases as we further define the roles and functions of IL-12 and IL-23. Research into the function and regulation of IL-12 and IL-23 is a promising area of study for inflammatory disease mediation, and inhibition of their actions may have clinical therapeutic applications.     

The immunoregulatory role of IL-35 in patients with interstitial lung disease

Pulmonary fibrosis involves various types of immune cells and soluble mediators, including TGF-β and IL-35, a recently identified heterodimeric cytokine that belongs to the IL-12 cytokine family. However, the effect of regulatory IL-35 may play an important role in fibrotic diseases. The aim of this paper is to explore the immunoregulatory role of IL-35 in the development of fibrosis in interstitial lung disease (ILD). To gain a better understanding of this issue, the concentrations of IL-35 and different profibrotic cytokines in fibrotic (F-ILD) and non-fibrotic (NF-ILD) patients by ELISA were compared to that of intracellular IL-35 and IL-17 on CD4+ T cells stimulated in the presence of BAL or with different ratios of recombinant IL-35 (rIL-35) and TGF-β (rTGF-β), which were evaluated by flow cytometry. We observed that BAL concentration of IL-35 was lower in F patients (p < 0.001) and was negatively correlated with concentrations of TGF-β (p < 0.001) and IL-17 (p < 0.001). In supplemented cell cultures, BAL from NF but not F patients enhanced the percentage of IL-35 + CD4+ T (p < 0.001) cells and decreased the percentage of IL-17 + CD4+ T cells (p < 0.001). The percentage of IL-35 + CD4+ T cells correlated positively with BAL concentration of IL-35 (p = 0.02), but correlated negatively with BAL concentrations of IL-17 (p = 0.007) and TGF-β (p = 0.01). After adjusting the concentrations of recombinant cytokines to establish a TGF-β: IL-35 ratio of 1:4, an enhanced percentage of IL-35 + CD4+ T cells (p < 0.001) but a decreased percentage of IL-17 + CD4+ T cells (p < 0.001) was observed. After adding recombinant IL-35 to the BAL from F patients until a 1:4 ratio of TGF-β: IL-35 was reached, a significantly increased percentage of IL-35 + CD4+ T cells (p < 0.001) and a decreased percentage of IL-17 + CD4+ T cells (p = 0.003) was found. These results suggest that IL-35 may induce an anti-fibrotic response, regulating the effect of TGF-β and the inflammatory response on CD4+ T cells. In addition, the TGF-β: IL-35 ratio in BAL has been shown to be a potential biomarker to predict the outcome of F patients with ILD.     

IL-35 Is Involved in the Pathogenesis of Guillain–Barré Syndrome Through Its Influence on the Function of CD4+ T Cells

CD4+ T cells and many cytokines play critical roles in the pathogenesis of Guillain–Barré Syndrome (GBS), an immune-mediated inflammatory disease. However, the role of IL-35, a novel member of the IL-12 cytokine family, in this kind of disease has not yet been elucidated. In this study, we investigated the functional changes of CD4+ T cells from GBS patients with IL-35 treatment in vitro. This study involved 21 GBS patients and an equal number of healthy controls (HCs). The results indicated that the average concentration of IL-35 in the plasma of GBS patients was lower than that of healthy controls (HCs). Increased levels of STAT1, STAT3 and STAT4 proteins and T-bet, ROR γt, IFN-γ and IL-17A mRNA were observed in CD4+ T cells from GBS patients. In contrast, the levels of STAT5 and STAT6 proteins and GATA3, Foxp3, IL-4 and TGF-β1 mRNAs were decreased in GBS patients in comparison with those of HCs. In addition, treatment of CD4+ T cells from GBS patients with IL-35 upregulated IL-35, STAT5 and STAT6 protein and T-bet, GATA3, Foxp3, IFN-γ, IL-4, IL-17A and TGF-β1 mRNA while inhibited levels of STAT3 and STAT4 protein and RORγt and IL-17A mRNA. These results indicate that IL-35 might play a potential role in GBS pathogenesis. Further studies are required in order to evaluate its role in GBS.     

卵巢癌患者外周血CD4+CD25hiCD127lo调节性T细胞格局变化及临床意义

目的:观察卵巢癌患者外周血中CD4+CD25hiCD127lo调节性T细胞格局变化及其相关免疫细胞因子TGF-β1、IL-10的变化及与临床病理特征之间的关系,探讨其临床意义.方法:采用流式细胞术(FCM)和酶联免疫吸附法(ELISA)检测70例卵巢癌患者、50例卵巢良性疾患及70例健康者外周血单个细胞中调节性T细胞的比率和血浆TGF-β1、IL-10的水平.结果:①卵巢癌患者外周血中CD4+CD25hiCD127loTreg调节性T细胞占CD4+细胞的比例为6.32%±1.46%(n=70),显著高于卵巢良性疾患4.03%±1.25%(n=50)和健康对照组3.21%±0.96%(n=70),均P＜0.01.术后患者CD4+CD25hiCD127loTreg比率与术前比较无明显差异.②卵巢癌患者血浆中TGF-β1、IL-10水平(256.68±56.34) pg /ml、(28.24±3.12) ng/ml,明显高于良性疾患(156.48±43.68) pg /ml、(20.58±2.39) ng/ml与健康对照组(130.24±35.60) pg/ml、(18.38±2.98) ng/ml,有统计学差异,分别P＜0.001,P＜0.01.③术前卵巢癌患者外周血CD4+CD25hiCD127loTreg比率、血浆中TGF-β1、IL-10水平与患者的临床分期、淋巴结转移以及远处转移有关,P＜0.05～P＜0.001.④相关分析显示,卵巢癌患者外周血 CD4+CD25hiCD127loTreg比率与血浆中TGF-β1水平、IL-10水平呈正相关,r=0.734,P＜0.01;r=0.665,P＜0.01.结论:①CD4+CD25hiCD127loTreg在卵巢癌患者外周血中表达显著增高,这可能是卵巢癌患者免疫功能下降的一个重要原因,并与临床病理特征存在显著相关性;②卵巢癌患者血浆中抑制性细胞因子TGF-β1、IL-10水平明显升高,并与临床病理特征存在显著相关性;③CD4+CD25hiCD127loTreg与TGF-β1、IL-10水平存在正相关,CD4+CD25hiCD127loTreg可能通过产生抑制性细胞因子TGF-β1、IL-10 对效应性T细胞发挥抑制作用.