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https://www.readbyqxmd.com/read/27933593/inflammation-induced-cd69-kupffer-cell-feedback-inhibits-t-cell-proliferation-via-membrane-bound-tgf-%C3%AE-1
#1
Xiang Zhang, Zhengping Jiang, Yan Gu, Yanfang Liu, Xuetao Cao, Yanmei Han
Kupffer cells, tissue-resident macrophage lineage cell, are enriched in vertebrate liver. The mouse F4/80(+) Kupffer cells have been subclassified into two subpopulations according to their phenotype and function: CD68(+) subpopulation with potent reactive oxygen species (ROS) production and phagocytic capacities, and CD11b(+) subpopulation with a potent capacity to produce T helper 1 cytokines. In addition, CD11b(+) Kupffer cells/macrophages may be migrated from the bone marrow or spleen, especially in inflammatory conditions of the liver...
December 6, 2016: Science China. Life Sciences
https://www.readbyqxmd.com/read/27933310/dynamics-of-antigen-presentation-to-transgene-product-specific-cd4-t-cells-and-of-treg-induction-upon-hepatic-aav-gene-transfer
#2
George Q Perrin, Irene Zolotukhin, Alexandra Sherman, Moanaro Biswas, Ype P de Jong, Cox Terhorst, Andrew M Davidoff, Roland W Herzog
The tolerogenic hepatic microenvironment impedes clearance of viral infections but is an advantage in viral vector gene transfer, which often results in immune tolerance induction to transgene products. Although the underlying tolerance mechanism has been extensively studied, our understanding of antigen presentation to transgene product-specific CD4(+) T cells remains limited. To address this, we administered hepatotropic adeno-associated virus (AAV8) vector expressing cytoplasmic ovalbumin (OVA) into wt mice followed by adoptive transfer of transgenic OVA-specific T cells...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27933292/nitric-oxide-modulates-postnatal-bone-marrow-derived-mesenchymal-stem-cell-migration
#3
John W Fuseler, Mani T Valarmathi
Nitric oxide (NO) is a small free-radical gas molecule, which is highly diffusible and can activate a wide range of downstream effectors, with rapid and widespread cellular effects. NO is a versatile signaling mediator with a plethora of cellular functions. For example, NO has been shown to regulate actin, the microfilament, dependent cellular functions, and also acts as a putative stem cell differentiation-inducing agent. In this study, using a wound-healing model of cellular migration, we have explored the effect of exogenous NO on the kinetics of movement and morphological changes in postnatal bone marrow-derived mesenchymal stem cells (MSCs)...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27932380/absence-of-vitamin-d-receptor-vdr-mediated-ppar%C3%AE-suppression-causes-alopecia-in-vdr-null-mice
#4
Vaibhav Saini, Hengguang Zhao, Elizabeth T Petit, Francesca Gori, Marie B Demay
Vitamin D receptor (VDR) mutations in humans and mice cause alopecia. VDR-null mice (VDR(-/-)) exhibit lack of postmorphogenic hair cycles as a result of impaired keratinocyte stem cell (KSC) function. To identify the molecular basis for abnormal KSC function, RNA sequencing of wild-type (WT) and VDR(-/-) KSCs was performed. These studies demonstrated that >80% of differentially expressed genes are up-regulated in VDR(-/-) KSCs; thus, the VDR is a transcriptional suppressor in WT KSCs. Peroxisome proliferator-activated receptor γ (PPARγ), PPARγ coactivator 1β (PGC1β), and lipoprotein lipase (LPL) were among the up-regulated genes identified...
December 8, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27932168/spindle-cell-lipoma-in-an-end-stage-renal-allograft-case-report
#5
Z Zhao, S Selvarajan, A L S Tiong, T H Lim, L Y Khor
BACKGROUND: Spindle cell lipoma is an uncommon variant of lipoma and usually occurs as a solitary, subcutaneous, and well circumscribed lesion in the posterior neck, shoulders, and back of older men. Primary renal lipomas are rarely reported. Spindle cell lipoma in the kidney has not been previously described in the literature. CASE REPORT: A 60-year-old Chinese man suffered graft failure 10 years after living related donor kidney transplantation. During cancer surveillance, he was found to have a mass in the renal allograft, which increased in size and was suspicious for renal cell carcinoma on computerized tomographic scan...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27932126/pretransplant-cd28-biomarker-levels-of-expression-and-quantification-of-molecules-per-cell-in-peripheral-cd4-t-cells-predicts-acute-rejection-episodes-in-liver-and-kidney-recipients
#6
F Boix, J M Bolarín, J Eguía, G Gonzalez-Martinez, J De La Peña, J A Galian, A M Hernández-Martínez, M R Moya-Quiles, I Legaz, J A Campillo, P Ramirez, F Sanchez-Bueno, A M García-Alonso, J A Pons, A Minguela, S Llorente, M Muro
BACKGROUND: Acute rejection (AR) remains a significant cause of graft loss. Better approaches to predict AR are being investigated. Surface CD28 protein is essential for T-cell proliferation and survival as well as cytokine production. PATIENTS AND METHODS: Pretransplant CD4(+)CD28(+) peripheral T cells were examined in 30 liver recipients (LRs) and 31 kidney recipients (KRs) by flow cytometry. RESULTS: Pretransplant CD4(+)CD28(+) T cells in LRs were significantly lower in rejectors than nonrejectors (P = ...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27930978/mechanism-of-action-and-effect-of-immune-modulating-agents-in-the-treatment-of-psoriasis
#7
Rehab M El-Gharabawy, Amira S Ahmed, Amal H Al-Najjar
OBJECTIVES: The aim of this work is to study the possible mechanisms through which different immune-modulating agents can produce their beneficial effects on treatment of psoriasis and to determine whether the supplementation of these agents for psoriasis patients induces regression of psoriasis. SUBJECTS AND METHODS: One hundred fifty participants were included in this study. The participants were divided into five groups: 1. Normal control group, 2. Psoriasis patients not taking any treatment, 3...
December 5, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27930879/melanoma-exosomes-deliver-a-complex-biological-payload-that-upregulates-ptpn11-to-suppress-t-lymphocyte-function
#8
Yueting Wu, Wentao Deng, Emily Chambers McGinley, David J Klinke
As exosomes are emerging as a new mode of intercellular communication, we hypothesized that the payload contained within exosomes is shaped by somatic evolution. To test this, we assayed the impact on primary CD8+ T cell function, a key mechanism for anti-tumor immunity, of exosomes derived from three melanoma-related cell lines. While morphologically similar, exosomes from each cell line were functionally different, as B16F0 exosomes dose-dependently suppressed T cell proliferation. In contrast, Cloudman S91 exosomes promoted T cell proliferation and Melan-A exosomes had a negligible effect on primary CD8+ T cells...
December 8, 2016: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/27930745/the-ebola-interferon-inhibiting-domains-attenuate-and-dysregulate-cell-mediated-immune-responses
#9
Ndongala Michel Lubaki, Patrick Younan, Rodrigo I Santos, Michelle Meyer, Mathieu Iampietro, Richard A Koup, Alexander Bukreyev
Ebola virus (EBOV) infections are characterized by deficient T-lymphocyte responses, T-lymphocyte apoptosis and lymphopenia. We previously showed that disabling of interferon-inhibiting domains (IIDs) in the VP24 and VP35 proteins effectively unblocks maturation of dendritic cells (DCs) and increases the secretion of cytokines and chemokines. Here, we investigated the role of IIDs in adaptive and innate cell-mediated responses using recombinant viruses carrying point mutations, which disabled IIDs in VP24 (EBOV/VP24m), VP35 (EBOV/VP35m) or both (EBOV/VP35m/VP24m)...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27929746/exogenous-expression-of-samhd1-inhibits-proliferation-and-induces-apoptosis-in-cutaneous-t-cell-lymphoma-derived-hut78-cells
#10
Karthik M Kodigepalli, Minghua Li, Shan-Lu Liu, Li Wu
Sterile alpha motif and HD domain-containing protein 1 (SAMHD1) is a mammalian dNTP hydrolase (dNTPase) that regulates intracellular dNTP balance. We have previously reported that SAMHD1 mRNA and protein levels are significantly downregulated in CD4(+) T-cells of patients with cutaneous T-cell lymphoma (CTCL), a disease characterized by infiltration of neoplastic CD4(+) T-lymphocytes into the skin. However, functional significance of SAMHD1 in CTCL development and progression remains unknown. Here we investigate the mechanism by which SAMHD1 induces apoptosis in CTCL-derived CD4(+) T-cells...
December 8, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27929420/tumor-microenvironment-metabolism-a-new-checkpoint-for-anti-tumor-immunity
#11
REVIEW
Nicole E Scharping, Greg M Delgoffe
When a T cell infiltrates a tumor, it is subjected to a variety of immunosuppressive and regulatory signals in the microenvironment. However, it is becoming increasingly clear that due to the proliferative and energetically-deregulated nature of tumor cells, T cells also operate at a metabolic disadvantage. The nutrient dearth of the tumor microenvironment (TME) creates "metabolic checkpoints" upon infiltrating T cells, impacting their ability to survive, proliferate and function effectively. In this review, we summarize the basics of tumor cell and T cell metabolism and discuss recent advances elucidating the individual metabolic checkpoints exerted on T cells that drive their dysfunction in the TME...
December 6, 2016: Vaccines
https://www.readbyqxmd.com/read/27927890/massively-increased-caries-susceptibility-in-an-irf6-cleft-lip-palate-model
#12
B Tamasas, T C Cox
Patients with cleft lip/palate (CLP) have been reported, in some studies, to exhibit an increased prevalence of caries, although the underlying cause for this increase is unknown. In genetically defined mouse models, studies of postnatal sequelae associated with CLP have been hampered by neonatal lethality. Using a conditional targeting approach, we ablated the major CLP gene Irf6 only in the late embryonic oral epithelium (Irf6 cKO), bypassing the role of the gene in lip and palate morphogenesis and thus ensuring survival to adulthood...
December 7, 2016: Journal of Dental Research
https://www.readbyqxmd.com/read/27927780/genomic-analysis-of-kidney-allograft-injury-identifies-hematopoietic-cell-kinase-as-a-key-driver-of-renal-fibrosis
#13
Chengguo Wei, Li Li, Madhav C Menon, Weijia Zhang, Jia Fu, Brian Kidd, Karen L Keung, Christopher Woytovich, Ilana Greene, Wenzhen Xiao, Fadi Salem, Zhengzi Yi, John Cijiang He, Joel T Dudley, Barbara Murphy
Renal fibrosis is the common pathway of progression for patients with CKD and chronic renal allograft injury (CAI), but the underlying mechanisms remain obscure. We performed a meta-analysis in human kidney biopsy specimens with CAI, incorporating data available publicly and from our Genomics of Chronic Renal Allograft Rejection study. We identified an Src family tyrosine kinase, hematopoietic cell kinase (Hck), as upregulated in allografts in CAI. Querying the Kinase Inhibitor Resource database revealed that dasatinib, a Food and Drug Administration-approved drug, potently binds Hck with high selectivity...
December 7, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27927767/t-cells-in-chronic-lymphocytic-leukemia-display-dysregulated-expression-of-immune-checkpoints-and-activation-markers
#14
Marzia Palma, Giusy Gentilcore, Kia Heimersson, Fariba Mozaffari, Barbro Näsman-Glaser, Emma Young, Richard Rosenquist, Lotta Hansson, Anders Österborg, Håkan Mellstedt
Chronic lymphocytic leukemia is characterized by impaired immune functions largely due to profound T cell defects. T cell functions also depend on co-signaling receptors, inhibitory or stimulatory, known as immune checkpoints, including cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and programmed death-1 (PD-1). Here we analyzed the T cell phenotype focusing on immune checkpoints and activation markers in chronic lymphocytic leukemia patients (n=80) with different clinical characteristics and compared to healthy controls...
December 7, 2016: Haematologica
https://www.readbyqxmd.com/read/27927642/an-expanded-population-of-pathogenic-regulatory-t-cells-in-giant-cell-arteritis-is-abrogated-by-il-6-blockade-therapy
#15
Chie Miyabe, Yoshishige Miyabe, Klemen Strle, Nancy D Kim, John H Stone, Andrew D Luster, Sebastian Unizony
OBJECTIVES: Randomised-controlled trials have recently proven the efficacy of the interleukin (IL)-6 receptor antagonist tocilizumab (TCZ) in giant cell arteritis (GCA). However, the mechanism of action of IL-6 blockade in this disease is unknown. Moreover, the role of regulatory T (Treg) cells in the pathogenesis of GCA remains underexplored. Given the plasticity of Tregs and the importance of IL-6 in their biology, we hypothesised that TCZ might modulate the Treg response in GCA. We therefore characterised the Treg compartment of patients with GCA treated with TCZ...
December 7, 2016: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/27926867/genomic-instability-is-induced-by-persistent-proliferation-of-cells-undergoing-epithelial-to-mesenchymal-transition
#16
Valentine Comaills, Lilian Kabeche, Robert Morris, Rémi Buisson, Min Yu, Marissa Wells Madden, Joseph A LiCausi, Myriam Boukhali, Ken Tajima, Shiwei Pan, Nicola Aceto, Srinjoy Sil, Yu Zheng, Tilak Sundaresan, Toshifumi Yae, Nicole Vincent Jordan, David T Miyamoto, David T Ting, Sridhar Ramaswamy, Wilhelm Haas, Lee Zou, Daniel A Haber, Shyamala Maheswaran
TGF-β secreted by tumor stroma induces epithelial-to-mesenchymal transition (EMT) in cancer cells, a reversible phenotype linked to cancer progression and drug resistance. However, exposure to stromal signals may also lead to heritable changes in cancer cells, which are poorly understood. We show that epithelial cells failing to undergo proliferation arrest during TGF-β-induced EMT sustain mitotic abnormalities due to failed cytokinesis, resulting in aneuploidy. This genomic instability is associated with the suppression of multiple nuclear envelope proteins implicated in mitotic regulation and is phenocopied by modulating the expression of LaminB1...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926489/suppression-of-immune-regulatory-cells-with-combined-therapy-of-celecoxib-and-sunitinib-in-renal-cell-carcinoma
#17
Qi Zhao, Jianming Guo, Guomin Wang, Yiwei Chu, Xiaoyi Hu
OBJECTIVE: To observe the the potential benefit of sunitinib in combination with cyclooxygenase-2(COX-2) inhibitor in renal cell carcinoma therapy. METHODS: 769-p cell lines were treated with sunitinib, celecoxib, or in combination at different concentrations respectively. We investigated the expression of granulocyte-macrophage colony stimulating factor (GM-CSF) in 769-p and cell proliferation in vitro. BALB/c mice implanted with Renca cells were divided into 4 groups and administered orally by gavage with sunitinib, COX-2 inhibitor (celecoxib) monotherapy or combination, and PBS respectively...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27925342/vascular-endothelial-growth-factor-g-405c-polymorphism-may-contribute-to-the-risk-of-developing-papillary-thyroid-carcinoma
#18
İlknur Bingül, Pervin Vural, Semra Doğru-Abbasoğlu, Esra Çil, Müjdat Uysal
BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. Vascular endothelial growth factor (VEGF) is a mediator implicated with cell proliferation, differentiation and migration, and monocyte/macrophage chemotaxis. In present study, we aimed to investigate the relationship between VEGF gene polymorphisms (G+405C, T-460C, and A-2578C) and PTC susceptibility. METHODS: DNA was isolated from peripheral blood leukocytes of 127 patients with PTC and 203 healthy controls...
December 7, 2016: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/27924981/hts-ftir-spectroscopy-allows-the-classification-of-polyphenols-according-to-their-differential-effects-on-the-mda-mb-231-breast-cancer-cell-line
#19
A Mignolet, V Mathieu, E Goormaghtigh
Breast cancer is a major public health issue among women in the world. Meanwhile new anticancer treatments struggle more and more to be accepted in the pharmaceutical market and research costs still increase. There is therefore a need to find new treatments and new screening methods to test them more quickly and efficiently. Among natural compounds, an increasing interest has been given to polyphenols as they can take action at the different stages of carcinogenesis, from tumour initiation to metastasis formation, by disturbing multiple cellular signalling pathways...
December 7, 2016: Analyst
https://www.readbyqxmd.com/read/27924833/tgf%C3%AE-2-induced-outflow-alterations-in-a-bioengineered-trabecular-meshwork-are-offset-by-a-rho-associated-kinase-inhibitor
#20
Karen Y Torrejon, Ellen L Papke, Justin R Halman, Magnus Bergkvist, John Danias, Susan T Sharfstein, Yubing Xie
Members of the transforming growth factor beta (TGFβ) cytokine family have long been associated with affecting several cellular functions, including cell proliferation, differentiation and extracellular matrix (ECM) turnover. Of particular interest to this work, TGFβ2 has been linked to most types of glaucomas as a potential fibrotic agent that can cause elevation of intraocular pressure (IOP). Given that the trabecular meshwork (TM) provides most of aqueous humor outflow resistance in the eye, an in vitro bioengineered human TM (HTM) model has been created and validated by analyzing effects of TGFβ2 on transcellular pressure changes and outflow facility...
December 7, 2016: Scientific Reports
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