Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.620
Filtrar
1.
Sci Rep ; 10(1): 2388, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32024923

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32031946

RESUMO

Caenorhabditis elegans (C. elegans) is a popular and excellent model for studies of aging due to its short lifespan. Methods for precisely measuring the physiological age of C. elegans are critically needed, especially for antiaging drug screening and genetic screening studies. The effects of various antiaging interventions on the rate of aging in the early stage of the aging process can be determined based on the quantification of physiological age. However, in general, the age of C. elegans is evaluated via human visual inspection of morphological changes based on personal experience and subjective judgment. For example, the rate of motor activity decay has been used to predict lifespan in early- to mid-stage aging. Using image processing, the physiological age of C. elegans can be measured and then classified into periods or classes from childhood to elderhood (e.g., 3 periods comprising days 0 - 2, 4 - 6 and 10 - 12) by using texture entropy (Shamir, L. et al., 2009). Our dataset consists of 913 microscopic images of C. elegans, with approximately 60 images per day from day 1 to day 14 of adulthood. We present quantitative methods to measure the physiological age of C. elegans with convolution neural networks (CNNs), which can measure age with a granularity of days rather than periods. The methods achieved a mean absolute error (MAE) of less than 1 day for the measured age of C. elegans. In our experiments, we found that after training and testing our dataset, 5 popular CNN models, 50-layer residual network (ResNet50), InceptionV3, InceptionResNetV2, 16-layer Visual Geometry Group network (VGG16) and MobileNet, measured the physiological age of C. elegans with an average testing MAE of 1.58 days. Furthermore, based on the results, we propose two models, one model for linear regression analysis and the other model for logistic regression, that combine a CNN model and a new attribute: curved_or_straight. The linear regression analysis model achieved a test MAE of 0.94 days; the logistic regression model achieved an accuracy of 84.78% with an error tolerance of 1 day.

3.
Eur J Cancer Prev ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32032153

RESUMO

Low-dose computed tomography lung cancer screening aims to detect early-stage lung cancers in order to decrease the incidence of advanced-stage lung cancers and to reduce lung cancer mortality. We analyzed the time trends of lung cancer stage distribution and mortality rates after the gradual implementation of the low-dose computed tomography lung cancer screening in a hospital-based cohort. Using the hospital-based cancer registry data on lung cancer number and death from 2007 to 2014, we aim to evaluate the trends in stage distribution and mortality rate after the gradual implementation of low-dose computed tomography lung cancer screening program over recent years. From 2007 to 2014, overall 2542 cases of lung cancers were diagnosed according to hospital-based cancer registry. For the 1-year mortality rate, the mortality rate decreased gradually from 48.16 to 37.04% between 2007 and 2014. For the 5-year mortality rate, the mortality rate decreased gradually from 88.49 to 69.44% between 2007 and 2014. There was a gradual decrease in stage IV lung cancer with the corresponding sharp increase in stage I early lung cancer after following the implementation of the large volume of the low-dose computed tomography examination between the years 2011 and 2014. In conclusion, these results suggest that the gradual implementation of low-dose computed tomography lung screening program could lead to a remarkable decrease in lung cancer mortality and a remarkable stage shift in the trend over time in this hospital-based cohort.

4.
J Drug Target ; : 1-51, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32037905

RESUMO

Cancer has become one of the major threats to human survival. Because of antibodies specificity and low toxicity, it is the primary choice to diagnose and treat cancer. It is easy to be cleared from the blood circulation or distributing throughout the body and causes unnecessary side effects. It is necessary to delivery antibodies to the tumour region in a stable, safe and effective manner. In this review, we discuss the latest studies that aimed to delivery antibodies to tumour sites via several vector forms, such as liposomes, carbon nanomaterials, and gold nanomaterials. How to deliver antibodies to the target site is a difficulty for antibody therapy. This review summarizes the antibody's therapeutic forms and carrier materials in recent years, and to explore how antibodies can be safely and stably delivered to the target site.

5.
Pain ; 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32040076

RESUMO

Morphine is a strong painkiller acting through mu opioid receptor (MOR). Full-length 7-transmembrane (TM) variants of MOR share similar amino acid sequences of TM domains in rodents and humans; however, interspecies differences in N- and C-terminal amino acid sequences of MOR splice variants dramatically affect the downstream signaling. Thus, it is essential to develop a mouse model that expresses human MOR splice variants for opioid pharmacological studies. We generated two lines of fully humanized MOR mice (hMOR; mMOR mice), line #1 and #2. The novel murine model having human OPRM1 genes and human-specific variants was examined by reverse transcription polymerase chain reaction (RT-PCR) and the MinION nanopore sequencing. The differences in the regional distribution of MOR between wild-type (WT) and humanized MOR mice brains were detected by RNAscope and radioligand binding assay. hMOR; mMOR mice were characterized in vivo using a tail-flick, charcoal meal, open field, tail suspension, naloxone precipitation tests, and rectal temperature measurement. The data indicated that WT and humanized MOR mice exhibited different pharmacology of morphine, including antinociception, tolerance, sedation, and withdrawal syndromes, suggesting the presence of species difference between mouse and human MORs. Therefore, hMOR; mMOR mice could serve as a novel mouse model for pharmacogenetic studies of opioids.

6.
Aging (Albany NY) ; 122020 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-32007952

RESUMO

The AKT/mTOR pathway is critical for bladder cancer (BC) pathogenesis and is hyper-activated during BC progression. In the present study, we identified a novel positive feedback loop involving oncogenic factors histone methyltransferase SMYD3, insulin-like growth factor-1 receptor (IGF-1R), AKT, and E2F-1. SMYD3 expression was significantly up-regulated in BC tumors and positively associated with histological grade, lymph node metastasis, and shorter patient survival. Depletion of SMYD3 inhibited BC cell proliferation, colony formation, migration, invasion, and xenograft tumor growth. Mechanistically, SMYD3 inhibition led to the diminished AKT/mTOR signaling activity, thereby triggering deleterious effects on BC cells. Furthermore, SMYD3 directly activates the expression of IGF-1R, a critical activator of AKT in BC, by inducing hyper-methylation of histone H3-K4 and subsequent chromatin remodeling in the IGF-1R promoter region. On the other hand, E2F-1, a downstream factor of the AKT pathway, binds to the E2F-1 binding motifs at the SMYD3 promoter and consequently induces SMYD3 transcription and expression. Thus, SMYD3/IGF-1R/AKT/E2F-1 forms a positive feedback loop leading to the hyper-activated AKT signaling. Our findings provide not only profound insights into SMYD3-mediated oncogenic activity but also present a unique avenue for treating BC by directly disrupting this signaling circuit.

7.
Ecotoxicol Environ Saf ; 192: 110250, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32028154

RESUMO

A bacterial strain designated Lysinibacillus fusiformis 15-4 was isolated from oil-free soil on the Qinghai-Tibet Plateau, which can grow well utilizing petroleum hydrocarbons as a carbon source at a lower temperature. To deeply characterize the molecular adaptations and metabolic processes of this strain when grown in a petroleum-containing environment, transcriptome analysis was performed. A total of 4664 genes and the expression of 3969 genes were observed in strain 15-4. When the strain was grown in petroleum-containing medium, 2192 genes were significantly regulated, of which 1312 (60%) were upregulated and 880 (40%) were downregulated. This strain degraded and adapted to petroleum via modulation of diverse molecular processes, including improvements in transporter activity, oxidoreductase/dehydrogenase activity, two-component system/signal transduction, transcriptional regulation, fatty acid catabolism, amino acid metabolism, and environmental stress responses. Many strain-specific genes were involved in the oxidation of hydrocarbon compounds, such as several luciferase family alkane monooxygenase genes, flavin-utilizing monooxygenase family genes, and flavoprotein-like family alkanesulfonate monooxygenase genes. Several cold shock protein genes were also induced suggesting adaptation to cold environments and the potential for petroleum degradation at low temperatures. The results obtained in this study may broaden our understanding of molecular adaptation of bacteria to hydrocarbon-containing environments and may provide valuable data for further study of L. fusiformis.

8.
Environ Pollut ; 260: 114096, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-32041035

RESUMO

Plastic mulching is suspected to be a significant source of microplastics in terrestrial environments owing to its intensive application and improper disposal. However, there has been a comparative lack of studies examining this hypothesis. In this study, the occurrence of macroplastics in agricultural soils was investigated by analysing 384 soil samples collected from 19 provinces across China. Additionally, the abundance of microplastics was investigated in potential hotspots that have carried out plastic mulching for over 30 years. Macroplastic concentrations in the soil samples ranged from 0.1 to 324.5 kg/ha, with an average of 83.6 kg/ha; the concentrations were higher in western China than in eastern China. A highly significant linear correlation (R2 = 0.61) was found between the consumption of mulching film and the plastic residue in soils, indicating plastic film mulching may be a major source of macroplastics. The abundances of microplastic particles increased over time in the locations where plastic mulching was continuously employed, with concentrations of 80.3 ± 49.3, 308 ± 138.1, and 1075.6 ± 346.8 pieces/kg soil in fields with 5, 15, and 24 y of continuous mulching, respectively. Fourier transform infrared analyses revealed that the composition of the microplastics matched that of the mulching films, suggesting the microplastic particles originated from the mulching films. These findings confirm that plastic mulching is an important source of macroplastic and microplastic contamination in terrestrial environments. Further studies to investigate the microplastic hazards in soils are thus necessary.

9.
Paediatr Drugs ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32020425

RESUMO

Therapeutic management of pustular psoriasis remains a challenge despite the rapid advance in psoriasis research and the development of drugs, especially biologics. Treatment guidelines have been established for pustular psoriasis, but no controlled studies are present for juvenile pustular psoriasis (JPP). Search of the literature reveals that current evidence of JPP treatment is limited to case reports and case series. Among the conventional drugs for JPP, oral retinoid is the most commonly used, yet concerns for growth disturbance exist. Cyclosporine and methotrexate have also been administered as first-line treatment. Etanercept is the first biological agent approved for juvenile plaque psoriasis, followed by adalimumab. However, infliximab is usually recommended for JPP because of the rapidity of onset, despite not being approved for use in pediatric psoriasis patients. More recently, secukinumab, ixekizumab, brodalumab, guselkumab, and risankizumab have been approved for adult pustular psoriasis in selected countries. Controlled studies are needed to prove the efficacy and long-term safety of the therapeutic treatments currently used for JPP.

10.
J Neurooncol ; 146(3): 417-426, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32020472

RESUMO

INTRODUCTION: The failure of immune checkpoint inhibitor (ICPi) on glioblastoma (GBM) treatment underscores the need for improving therapeutic strategy. We aimed to change tumor associated macrophage (TAM) from M2 type (anti-inflammatory) to M1 (pro-inflammatory) type to increase the therapeutic response of ICPi. We proposed that combined rapamycin (R) and hydroxychloroquine (Q) preferentially induce M2 cells death, as fatty acid oxidation was their major source of energy. METHODS: Macrophage polarization was characterized on mice and human macrophage cell lines by specific cytokines stimulation with or without RQ treatment under single culture or co-culture with GBM cell lines. Tumor sizes were evaluated on subcutaneous and intracranial GL261 mice models with or without RQ, anti-PD1 mAb treatment. Tumor volumes assessed by MRI scan and proportions of tumor infiltrating immune cells analyzed by flow cytometry were compared. RESULTS: In vitro RQ treatment decreased the macrophages polarization of M2, increased the phagocytic ability, and increased the lipid droplets accumulation. RQ treatment decreased the expression levels of CD47 and SIRPα on tumor cells and macrophage cells in co-culture experiments. The combination of RQ and anti-PD1 treatment was synergistic in action. Enhanced the intra-tumoral M1/M2 ratio, the CD8/CD4 ratio in the intracranial GL261 tumor model after RQ treatment were evident. CONCLUSION: We provide a rationale for manipulating the macrophage phenotype and increased the therapeutic effect of ICPi. To re-educate and re-empower the TAM/microglia opens an interesting avenue for GBM treatment.

11.
Bosn J Basic Med Sci ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32020847

RESUMO

Genetic factors play an important role in the pathogenesis of ischemic stroke. Of these, epigenetic modifications provide a new direction for the study of ischemic stroke pathogenesis. This study aimed to determine the correlation between DNA methylation of the gene encoding S-adenosylhomocysteine hydrolase (AHCY) and the risk of ischemic stroke in 64 ischemic stroke patients and 138 patients with traumatic brain injury (control group). The methylation level of AHCY was analyzed using quantitative methylation-specific polymerase chain reaction. Statistically significant differences in AHCY methylation levels were observed between the case group [medians (interquartile range): 0.13% (0.09%, 0.27%)] and the control group [0.06% (0.00%, 0.17%), p < 0.0001], and these associations remained significant in both male (p = 0.003) and female (p = 0.0005) subjects. A subgroup analysis by age revealed a considerably higher percentage of methylated AHCY in the case group than the control group in all age groups (age < 60 years, p = 0.007; age ≥ 60 years, p < 0.0001). A receiver operating characteristic (ROC) curve analysis revealed a trend toward a role for AHCY methylation as an indicator of risk in all ischemic patients [area under the curve (AUC) = 0.70, p = 0.0001], male patients (AUC = 0.67, p = 0.004), and female patients (AUC = 0.75, p = 0.0002). Our study confirmed a significant association between the AHCY DNA methylation level and the risk of ischemic stroke, suggesting that this gene methylation pattern may be a potential diagnostic marker of ischemic stroke.

12.
World J Surg ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32040606

RESUMO

BACKGROUND AND OBJECTIVE: This study aimed to investigate the relationship between bleb formation, primary spontaneous pneumothorax (PSP) and pectus excavatum (PE). METHODS: From July 2005 to December 2016, the records of 514 patients with PE who underwent the Nuss procedure were obtained from a prospectively collected database and reviewed. Clinical features, images and treatments were analyzed retrospectively. RESULTS: The incidence rate of bleb formation was 26.5% in PE patients. The bleb group had a greater body height (174.4 cm vs. 170.4 cm, p < 0.001), a higher Haller index (HI; 4.2 vs. 3.43, p < 0.001) and a higher risk of developing PSP than the non-bleb group (risk ratio 9.8, p = 0.002). HI values larger than 3.615 had good discriminatory power for predicting bleb formation in patients with PE. With each increase in the HI, PE patients had a 2.2-fold greater odds ratio of bleb formation (odds ratio 2.221, CI 1.481-3.330, p < 0.001). CONCLUSION: We discovered that a high percentage of PE patients have bleb formation and a higher risk of PSP, especially those with an HI >3.615. High-resolution computed tomography of the chest may be useful for evaluating both the HI and the presence of blebs in the lungs before performing a corrective surgical procedure.

13.
Curr Genet ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32040734

RESUMO

Serine/arginine (SR) proteins play significant roles in pre-mRNA splicing in eukaryotes. To investigate how gene expression influences fungal development and pathogenicity in Fusarium graminearum, a causal agent of Fusarium head blight (FHB) of wheat and barley, our previous study identified a SR protein FgSrp1 in F. graminearum, and showed that it is important for conidiation, plant infection and pre-mRNA processing. In this study, we identified another SR protein FgSrp2 in F. graminearum, which is orthologous to Schizosaccharomyces pombe Srp2. Our data showed that, whereas yeast Srp2 is essential for growth, deletion of FgSRP2 resulted in only slight defects in vegetative growth and perithecia melanization. FgSrp2 localized to the nucleus and both its N- and C-terminal regions were important for the localization to the nucleus. FgSrp2 interacted with FgSrp1 to form a complex in vivo. Double deletion of FgSRP1 and FgSRP2 revealed that they had overlapping functions in vegetative growth and sexual reproduction. RNA-seq analysis revealed that, although deletion of FgSRP2 alone had minimal effects, deletion of both FgSRP1 and FgSRP2 caused significant changes in gene transcription and RNA splicing. Overall, our results indicated that FgSrp2 regulates vegetative growth, sexual reproduction and pre-mRNA processing by interacting with FgSrp1.

14.
Infect Immun ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32041786

RESUMO

Cellular membrane proteins are a critical part of the host defense mechanisms against infection and intracellular survival of Listeria monocytogenes The complex spatiotemporal regulation of bacterial infection by various membrane proteins has been challenging to study. Here, using mass spectrometry analyses, we depicted the dynamic expression landscape of membrane proteins upon L. monocytogenes infection in dendritic cells. We showed that Dynein light chain 1 (Dynll1) formed a persistent complex with the mitochondrial cytochrome oxidase, Cox4i1 that is disturbed by pathogen insult. We discovered that the dissociation of the Dynll1-Cox4i1 complex is required for the release of mitochondrial reactive oxygen species and serves as a regulator of intracellular proliferation of Listeria monocytogenes Our study shows that Dynll1 is an inhibitor of mitochondrial reactive oxygen species and can serve as a potential molecular drug target for antibacterial treatment.

15.
Biomed Environ Sci ; 33(1): 37-47, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-32029057

RESUMO

Objective: To evaluate the effects of incretin-based therapies on body weight as the primary outcome, as well as on body mass index (BMI) and waist circumference (WC) as secondary outcomes. Methods: Databases including Medline, Embase, the Cochrane Library, and clinicaltrials.gov (www.clinicaltrials.gov) were searched for randomized controlled trials (RCTs). Standard pairwise meta-analysis and network meta-analysis (NMA) were both carried out. The risk of bias (ROB) tool recommended by the Cochrane handbook was used to assess the quality of studies. Subgroup analysis, sensitivity analysis, meta-regression, and quality evaluation based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) were also performed. Results: A total of 292 trials were included in this study. Compared with placebo, dipeptidyl-peptidase IV inhibitors (DPP-4Is) increased weight slightly by 0.31 kg [95% confidence interval ( CI): 0.05, 0.58] and had negligible effects on BMI and WC. Compared with placebo, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) lowered weight, BMI, and WC by -1.34 kg (95% CI: -1.60, -1.09), -1.10 kg/m 2 (95% CI: -1.42, -0.78), and -1.28 cm (95% CI: -1.69, -0.86), respectively. Conclusion: GLP-1 RAs were more effective than DPP-4Is in lowering the three indicators. Overall, the effects of GLP-1 RAs on weight, BMI, and WC were favorable.

16.
Sci Rep ; 10(1): 2006, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32029840

RESUMO

The prognostic factors of patients who undergo radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is not fully elucidated. We aimed to investigate the role of liver stiffness (LS) and spleen stiffness (SS) measured by acoustic radiation force impulse (ARFI) elastography in determining the prognoses of patients with HCC after RFA. We prospectively enrolled 173 patients with HCC who underwent ARFI elastography for measurement of LS and SS on the same day of RFA. Overall survival (OS), recurrence-free survival (RFS) after adjusting for competing mortality, and presence of hepatic decompensation were investigated. Patients with LS > 1.5 m/s had significantly shorter OS and RFS than their counterparts. Anti-viral treatment (hazard ratio [HR]: 0.396, p = 0.015) and LS > 1.5 m/s (HR 4.105, p = 0.028) correlated with OS by a multivariate analysis. Besides, serum alpha fetoprotein >10 ng/mL and LS > 1.5 m/s independently predicted poorer RFS. On the other hand, anti-viral treatment (HR: 0.315, p = 0.010), creatinine > 1.5 mg/dL (HR: 9.447, p = 0.006), and SS > 2.7 m/s (HR: 2.869, p = 0.044) predicted a higher risk of hepatic decompensation. In conclusion, LS but not SS measured by ARFI elastography predicted tumor recurrence and OS in RFA-treated HCC; whereas, SS predicted development of hepatic decompensation in these patients.

17.
Dig Dis Sci ; 2020 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-31955286

RESUMO

BACKGROUND: Diabetes mellitus (DM) is common in patients with hepatocellular carcinoma (HCC) and may impact survival. Very few studies focused on the influence of DM in different clinical scenarios. We evaluated the prognostic impact of DM on HCC patients stratified by liver dysfunction, Milan criteria, and performance status defined in the Barcelona Clínic Liver Cancer staging parameters. METHODS: A prospective dataset of 3573 HCC patients between 2002 and 2016 was retrospectively analyzed. The multivariate Cox proportional hazards model was used to identify independent prognostic predictors. The Kaplan-Meier method with a log-rank test was applied to compare the survival distributions between different patient groups. RESULTS: Among all, DM was not an independent prognostic predictor in the Cox multivariate analysis (p = 0.1044). In the subgroup analysis, DM was not a significant prognostic predictor in Child-Turcotte-Pugh class A or class B/C patients. However, DM was associated with a decreased survival in patients within the Milan criteria (hazard ratio [HR] 1.36, 95% confidence interval [CI] 1.155-1.601, p = 0.0002) and in those with the performance status 0 (HR 1.213, 95% CI 1.055-1.394, p = 0.0067) in the multivariate Cox analysis, but not in those beyond the Milan criteria and poor performance status. CONCLUSIONS: DM is highly prevalent in HCC patients and has a distinct survival impact. DM is an independent survival predictor among patients within the Milan criteria and good performance status. These high-risk patients should be closely monitored, and aggressive anticancer treatment should be considered.

18.
FASEB J ; 34(2): 2055-2074, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31908016

RESUMO

In spinal cord ischemia-reperfusion (I/R) injury, large amounts of reactive oxygen species can cause mitochondrial damage. Therefore, mitophagy acts as the main mechanism for removing damaged mitochondria and protects nerve cells. This study aimed to illustrate the important role of GPCR kinase 2-interacting protein-1 (GIT1) in mitophagy in vivo and in vitro. The level of mitophagy in the neurons of Git1 knockout mice was significantly reduced after ischemia-reperfusion. However, the overexpression of adeno-associated virus with Git1 promoted mitophagy and inhibited the apoptosis of neurons. GIT1 regulated the phosphorylation of Beclin-1 in Thr119, which could promote the translocation of Parkin to the mitochondrial outer membrane. This process was independent of PTEN-induced kinase 1 (PINK1), but it could not rescue the role in the absence of PINK1. Overall, GIT1 enhanced mitophagy and protected neurons against ischemia-reperfusion injury and, hence, might serve as a new research site for the protection of ischemia-reperfusion injury.

19.
Immunol Cell Biol ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919905

RESUMO

Epicutaneous (EC) sensitization with protein allergens is the most important sensitization route for atopic dermatitis. Plasmacytoid dendritic cells (pDCs) are characterized by massive secretion of interferon-α (IFNα). B6 mice are T helper type 1 (Th1)-prone and are representative of non-atopic humans, whereas BALB/c mice are Th2-prone and are representative of atopic humans. Here, we show that naïve BALB/c mice contain a greater number of nonactivated pDCs in peripheral lymph nodes (LNs) than do naïve B6 mice. Naïve BALB/c mice also have more of the CD8α- subset in LNs than naïve B6 mice. Moreover, in vivo depletion of pDCs during EC sensitization results in enhanced Th2 responses in BALB/c mice, but not in B6 mice. Mechanistically, when BALB/c mice undergo EC sensitization, there is an increase in pDCs entering draining LNs. These cells exhibit modest activation including comparable costimulation expression but increased cytokine expression compared with those of naïve mice. In vivo depletion of pDCs during EC sensitization significantly increases the activation of dermal dendritic cells (dDCs) suggesting a regulatory effect on these cells. To this end, a suppressive effect of pDCs on conventional dendritic cells was also demonstrated in vitro. Further, in vivo blockade of IFNα by an anti-IFNAR antibody (Ab) or in vivo reduction of IFNα production of pDCs by anti-siglec-H Ab both resulted in enhanced activation of dDCs. Collectively, our results demonstrate that pDCs suppress Th2 responses induced by EC sensitization via IFNα-mediated regulation of dDCs.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA