Indoleamine 2,3-dioxygenase regulates T cell activity through Vav1/Rac pathway

Publication date: January 2017
Source:Molecular Immunology, Volume 81
Author(s): Runmei Li, Hui Li, Qian Sun, Liang Liu, Chen Zhang, Xiubao Ren
The immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) suppresses T-cell responses and promotes immune tolerance in tumor resistance. A previous study determined that IDO inhibits Vav1 mRNA expression and the activation of Vav1 and its downstream targets in T cells in the guanine exchange factor (GEF)-independent pathway. The current study aims to determine whether IDO induces T-cell immunosuppression through Vav1/Rac signaling pathway, which is a GEF-dependent pathway. The correlation between Vav1 mRNA expressions in T cells of tumor infiltrating lymphocytes and the levels of IDO expression in lung cancer tissues from lung cancer patients was detected. HEK293 cells were stably transfected with human IDO (HEK293-IDO). T cells were isolated from human blood. HEK293-IDO cells were co-incubated with T cells in the presence or absence of an anti-CD3 antibody to activate T cell receptor (TCR) and/or 1-methyl-l-tryptophan (1-MT) to inhibit IDO activity. The early signaling proteins in T-cytoskeleton regulation through Vav1/Rac pathway of T cell were determined. A significant and negative correlation was observed between IDO and Vav1 expression in the tumor microenvironment. IDO, which was produced by HEK293-IDO cells, significantly inhibited the expression of Vav1, which resulted in defective F-actin reorganization. Thus, TCR signaling initiation was damaged. The effects on T-cells induced by the co-culture of HEK293-IDO cells with T cells were attenuated by 1-MT. Results indicate that the inhibitory effects of IDO on T cell immune responses may occur through the down-regulation of Vav1 protein expression and the suppression of Vav1/Rac cascade. These studies provide insight into the mechanisms of immune escape induced by IDO.



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Indoleamine 2,3-dioxygenase regulates T cell activity through Vav1/Rac pathway

Publication date: January 2017
Source:Molecular Immunology, Volume 81
Author(s): Runmei Li, Hui Li, Qian Sun, Liang Liu, Chen Zhang, Xiubao Ren
The immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) suppresses T-cell responses and promotes immune tolerance in tumor resistance. A previous study determined that IDO inhibits Vav1 mRNA expression and the activation of Vav1 and its downstream targets in T cells in the guanine exchange factor (GEF)-independent pathway. The current study aims to determine whether IDO induces T-cell immunosuppression through Vav1/Rac signaling pathway, which is a GEF-dependent pathway. The correlation between Vav1 mRNA expressions in T cells of tumor infiltrating lymphocytes and the levels of IDO expression in lung cancer tissues from lung cancer patients was detected. HEK293 cells were stably transfected with human IDO (HEK293-IDO). T cells were isolated from human blood. HEK293-IDO cells were co-incubated with T cells in the presence or absence of an anti-CD3 antibody to activate T cell receptor (TCR) and/or 1-methyl-l-tryptophan (1-MT) to inhibit IDO activity. The early signaling proteins in T-cytoskeleton regulation through Vav1/Rac pathway of T cell were determined. A significant and negative correlation was observed between IDO and Vav1 expression in the tumor microenvironment. IDO, which was produced by HEK293-IDO cells, significantly inhibited the expression of Vav1, which resulted in defective F-actin reorganization. Thus, TCR signaling initiation was damaged. The effects on T-cells induced by the co-culture of HEK293-IDO cells with T cells were attenuated by 1-MT. Results indicate that the inhibitory effects of IDO on T cell immune responses may occur through the down-regulation of Vav1 protein expression and the suppression of Vav1/Rac cascade. These studies provide insight into the mechanisms of immune escape induced by IDO.



http://ift.tt/2g604z7

Trend analysis of CO2 and CH4 recorded at a semi-natural site in the northern plateau of the Iberian Peninsula

Publication date: February 2017
Source:Atmospheric Environment, Volume 151
Author(s): Isidro A. Pérez, M. Luisa Sánchez, M. Ángeles García, Nuria Pardo
CO2 and CH4 were recorded from October 2010 to February 2016 with a Picarro G1301 analyser at the centre of the upper plateau of the Iberian Peninsula. Large CO2 values were observed during the vegetation growing season, and were reinforced by the stable boundary layer during the night. Annual CH4 evolution may be explained by ecosystem activity and by the dispersion linked with the evolution of the boundary layer. Their trends were studied using an equation that considers one polynomial and one harmonic part. The polynomial part revealed an increasing trend from 0.8 to 2.3 ppm year⁻¹ for CO2 and from 0.004 to 0.011 ppm year⁻¹ for CH4. The harmonic part considered four harmonics whose amplitudes were noticeable for the first and second harmonics for CO2 and for the first harmonic for CH4. Long-term evolution was similar with alternative equations. Finally, seasonal study indicated summer minima for both gases, which may be explained by the lack of vegetation in this season. Harmonic analysis showed two maxima for CO2, one in spring linked with vegetation growth, which decreased with time, and another in autumn related with the onset of plant activity after the summer, which increased with time. CH4 presented only one maximum in winter and a short time with steady concentration in spring where the evolution of the boundary layer may play a noticeable role. The harmonic equation, which takes into account all the observations, revealed opposite behaviour between CO2, whose minima decreased, and CH4, whose maxima increased.



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Commentary on: “The DanCavas Pilot Study of Multifaceted Screening for Subclinical Cardiovascular Disease in Men and Women Aged 65–74 Years”

Publication date: Available online 5 December 2016
Source:European Journal of Vascular and Endovascular Surgery
Author(s): J.T. Powell




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Improved Cognitive and Memory Abilities in a Patient With Alzheimer’s Disease Treated with Activated Immune Cells: Immune Cell Therapy May Benefit More Ad Patients

Publication date: Available online 5 December 2016
Source:Medical Hypotheses
Author(s): B. Laumbacher, B. Fellerhoff-Loesch, R. Wank
So far, the pathogenesis of Alzheimer's disease (AD) has not been clarified, nor has patient therapy been satisfactory. Although inheritance dominates the less frequent early-onset AD in young and middle-aged individuals, environmental and immunogenetic factors have been identified in the most frequently occurring late-onset AD of higher-aged individuals, comprising 90% of AD patients. Thorough investigations have detected a prevalence of certain microbes which are known to affect brain activities in the brains of AD patients. This microbial prevalence suggests failing immune responses by immune gene variants against specific microbes. In fact, some immune gene variants have been detected significantly more often in AD patients. Failing immune responses can be corrected by activating immune cells outside the body ("in vitro") for the subsequent therapeutical injections. Activated immune cells digest and present microbial peptides better and differentiate naïve/resting immune cells to powerful effector cells, which can be used for therapy. The patient's activated immune cells can pass the blood–brain barrier and overcome chronic infections in the brain. Furthermore, activated immune cells can secrete a series of neurotrophins for the restoration of neuronal circuits. Based on the encouraging results of immunotherapy in a patient with late-onset AD, we hypothesize that therapy with the patient́s activated immune cells would safely benefit many AD patients.



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Effects of ovarian ablation or suppression in premenopausal breast cancer: A meta-analysis of randomized controlled trials

Publication date: Available online 5 December 2016
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Pan Zhang, Chang-Zai Li, Gui-Mei Jiao, Jin-Ji Zhang, Hui-Ping Zhao, Feng Yan, Shi-Feng Jia, Bao-Shan Hu, Chun-Tao Wu
BackgroundThe effect of ovarian ablation or suppression (OAS) in premenopausal women with breast cancer is controversial. In this study, the overall survival (OS), disease-free survival (DFS) and adverse event of OAS versus no OAS were compared.MethodsA literature review of EMBASE, Web of Science, PUBMED, and Cochrane Library were conducted. The hazard ratio (HR) and 95% confidence interval (CI) for OS and DFS, as well as risk ratio (RR) and 95% CI for adverse events were evaluated. I-squared statistic (I²) represents heterogeneity. Review Manager 5.3 was used to analyze the data.ResultsTwenty-nine studies with a total of 21249 women were included. In premenopausal women aged 40 years or younger, there were significant differences in OS (HR 0.78, 95% CI: 0.66–0.94, P=0.008, I²=0%) and DFS (HR 0.84, 95% CI: 0.73–0.97, P=0.02, I²=0%) between OAS and no OAS. In advanced stage breast cancer, a significant difference was found in OS (HR 0.76, 95% CI: 0.60–0.96, P=0.02, I²=0%), but there was no significant difference in DFS (HR 0.82, 95% CI: 0.50–1.33, P=0.41), with significant heterogeneity (P=0.16, I²=50%). Patients treated with OAS had more chances to have hot flushes (RR 1.91, 95% CI: 1.62–2.26, p<0.01, I²=0%) and vaginal dryness (RR 1.19, 95% CI: 1.08–1.31, P=0.0003, I²=0%). No significant difference in depression (RR 1.28, 95% CI: 0.94–1.74, P=0.12, I²=0%).ConclusionsThe study shows that OAS plays a beneficial role in premenopausal women aged40 years or younger and advanced stage breast cancer. However, OAS is associated with increase in hot flushes and vaginal dryness. There is potential publication bias. Further randomized evidence is needed.



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High-resolution three-dimensional quantitative map of the macromolecular proton fraction distribution in the normal rat brain

Publication date: Available online 5 December 2016
Source:Data in Brief
Author(s): Anna V. Naumova, Andrey E. Akulov, Marina Yu. Khodanovich, Vasily L. Yarnykh
The presented dataset provides a normative high-resolution three-dimensional (3D) macromolecular proton fraction (MPF) map of the healthy rat brain in vivo and source images used for its reconstruction. The images were acquired using the protocol described elsewhere (Naumova, et al. High-resolution three-dimensional macromolecular proton fraction mapping for quantitative neuroanatomical imaging of the rodent brain in ultra-high magnetic fields. Neuroimage (2016) doi: 10.1016/j.neuroimage.2016.09.036). The map was reconstructed from three source images with different contrast weightings (proton density, T1, and magnetization transfer) using the single-point algorithm with a synthetic reference image. Source images were acquired from a living animal on an 11.7T small animal MRI scanner with isotropic spatial resolution of 170µm³ and total acquisition time about 1.5h. The 3D dataset can be used for multiple purposes including interactive viewing of rat brain anatomy, measurements of reference MPF values in various brain structures, and development of image processing techniques for the rodent brain segmentation. It also can serve as a gold standard image for implementation and optimization of rodent brain MRI protocols.



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