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Ryan D Sheldon, Kayla M Kanosky, Kevin D Wells, Lili Miles, James W Perfield, Stavra Xanthakos, Thomas H Inge, R Scott Rector
BACKGROUND: Mechanisms responsible for progression of nonalcoholic fatty liver disease (NAFLD) to steatohepatitis (NASH) remain poorly defined. METHODS: To examine the potential contribution of adipose tissue to NAFLD progression, we performed a complete transcriptomic analysis using RNA-sequencing (RNA-seq) on intra-abdominal adipose tissue (IAT) from severely obese adolescents (Mage 16.9±0.4 yrs; BMI z-score 2.7±0.1) undergoing bariatric surgery and liver biopsy categorized into 3 groups; No steatosis (Normal, n=8), steatosis only (n=13), or NASH (n=10) by liver histology...
October 7, 2016: Physiological Genomics
Lauren Brasile, Nicholas Henry, Bart Stubenitsky
BACKGROUND: We have previously reported on a novel organ-specific immunomodifying therapy that provides protection from early allograft rejection in the absence of systemic immunosuppressive drugs. This novel therapy is a nano-barrier membrane called ImmunoCloak, consisting of a matrix of laminin, proteoglycans, fibronectin and collagens. The membrane "immunocloaks" the luminal surfaces within the renal vasculature by covering the point of contact between donor vascular endothelial cells and the recipient's immune cells; without adversely affecting renal function...
October 19, 2016: Transplantation
Peter Bailey, David K Chang, Marie-Andrée Forget, Francis A San Lucas, Hector A Alvarez, Cara Haymaker, Chandrani Chattopadhyay, Sun-Hee Kim, Suhendan Ekmekcioglu, Elizabeth A Grimm, Andrew V Biankin, Patrick Hwu, Anirban Maitra, Jason Roszik
Immunotherapy approaches for pancreatic ductal adenocarcinoma (PDAC) have met with limited success. It has been postulated that a low mutation load may lead to a paucity of T cells within the tumor microenvironment (TME). However, it is also possible that while neoantigens are present, an effective immune response cannot be generated due to an immune suppressive TME. To discern whether targetable neoantigens exist in PDAC, we performed a comprehensive study using genomic profiles of 221 PDAC cases extracted from public databases...
October 20, 2016: Scientific Reports
Yan Xiong, Xiangfang Tang, Qingshi Meng, Hongfu Zhang
Ammonia has been considered the contaminant primarily responsible for respiratory disease in poultry. Even though it can cause tracheal lesions, its adverse effects on the trachea have not been sufficiently studied. The present study investigated tracheal changes in Arbor Acres broilers (Gallus gallus) induced by high concentration of ammonia using isobaric tag for relative and absolute quantification (iTRAQ)-based proteome analysis. In total, 3,706 proteins within false discovery rate of 1% were identified, including 119 significantly differentially expressed proteins...
October 17, 2016: Science China. Life Sciences
M L V Azevedo, N B Bonan, G Dias, F Brehm, T M Steiner, W M Souza, A E M Stinghen, F C Barreto, Selene Elifio-Esposito, R Pecoits-Filho, A N Moreno-Amaral
Immune system dysfunction is a common condition in chronic kidney disease (CKD). The present study investigated the effect of p-Cresyl sulfate (pCS) on human cell line U937 monocyte-derived macrophages (MDM) activity. MDM (1×10(6) cells/mL) were incubated with pCS (10, 25, or 50μg/mL), with or without lipopolysaccharide (LPS; 25ng/mL) and then evaluated NO production, phagocytosis and antigen-presenting molecules expression (HLA-ABC, HLA-DR, CD80 and CD86). All analyses were performed by flow cytometry. All pCS concentrations were able to increase NO production (49±12...
October 16, 2016: Toxicology Letters
Yoshie Kametani, Shino Ohshima, Asuka Miyamoto, Atsuko Shigenari, Masaki Takasu, Noriaki Imaeda, Tatsuya Matsubara, Masafumi Tanaka, Takashi Shiina, Hiroshi Kamiguchi, Ryuji Suzuki, Hitoshi Kitagawa, Jerzy K Kulski, Noriaki Hirayama, Hidetoshi Inoko, Asako Ando
The class I major histocompatibility complex (MHC) presents self-developed peptides to specific T cells to induce cytotoxity against infection. The MHC proteins are encoded by multiple loci that express numerous alleles to preserve the variability of the antigen-presenting ability in each species. The mechanism regulating MHC mRNA and protein expression at each locus is difficult to analyze because of the structural and sequence similarities between alleles. In this study, we examined the correlation between the mRNA and surface protein expression of swine leukocyte antigen (SLA)-1*0401 after the stimulation of peripheral blood mononuclear cells (PBMCs) by Staphylococcus aureus superantigen toxic shock syndrome toxin-1 (TSST-1)...
2016: PloS One
Sarah A Overall, Dorothée Bourges, Ian R van Driel, Paul A Gleeson
How the immune system maintains peripheral tolerance under inflammatory conditions is poorly understood. Here we assessed the fate of gastritogenic T cells following inflammatory activation in vivo. Self-reactive T cells (A23 T cells) specific for the gastric H(+) /K(+) ATPase α subunit (HKα) were transferred into immunosufficient recipient mice and immunised at a site distant to the stomach with adjuvant containing the cognate HKα peptide antigen. Activation of A23 T cells by immunisation did not impact on either immune tolerance or protection from gastric autoimmunity in wild-type BALB/c mice...
October 19, 2016: European Journal of Immunology
Bagirath Gangadharan, Mathieu Ing, Sandrine Delignat, Ivan Peyron, Maud Teyssandier, Srinivas V Kaveri, Sébastien Lacroix-Desmazes
The development of inhibitory antibodies to therapeutic FVIII is the major complication of replacement therapy in patients with hemophilia A. The first step in the initiation of the anti-FVIII immune response is FVIII interaction with receptor(s) on antigen-presenting cells followed by endocytosis and presentation to naive CD4+ T cells. Recent studies indicate a role for the C1 domain in FVIII uptake. We investigated whether charged residues in the C2 domain participate in immunogenic FVIII uptake. Co-incubation of FVIII with BO2C11, a monoclonal C2-specific IgG, reduced FVIII endocytosis by dendritic cells and presentation to CD4+ T cells, and diminished FVIII immunogenicity in FVIII-deficient mice...
October 6, 2016: Haematologica
Emilie Duvallet, Mathilde Boulpicante, Takahiro Yamazaki, Chrysoula Daskalogianni, Rodrigo Prado Martins, Sonia Baconnais, Bénédicte Manoury, Robin Fahraeus, Sébastien Apcher
Cellular immune reactions against non-self-epitopes require activation of cytotoxic CD8(+) T-cells via cross-presentation of MHC class I-restricted peptides by professional antigen presenting cells (pAPCs), with the consequent detection and elimination of cells expressing the same antigens via the endogenous (direct) pathway. The source of peptides for the endogenous pathway is constituted of alternative mRNA translation products; however, it is still unclear which source of peptides is used for cross-presentation...
2016: Oncoimmunology
Marie de Charette, Aurélien Marabelle, Roch Houot
Downregulation/loss of the antigen presentation is a major immune escape mechanism in cancer. It allows tumour cells to become 'invisible' and avoid immune attack by antitumour T cells. In tumour harbouring properties of professional antigen presenting cells (i.e. tumour B cells in lymphoma), downregulation/loss of the antigen presentation may also prevent direct priming of naïve T cells by tumour cells. Here, we review treatments that may induce/restore antigen presentation by the tumour cells. These treatments may increase the generation of antitumour T cells and/or their capacity to recognise and eliminate tumour cells...
October 15, 2016: European Journal of Cancer
Venetia Bigley, Dawn Barge, Matthew Collin
PURPOSE OF REVIEW: Dendritic cells are specialized antigen-presenting cells which link innate and adaptive immunity, through recognition and presentation of antigen to T cells. Although the importance of dendritic cells has been demonstrated in many animal models, their contribution to human immunity remains relatively unexplored in vivo.Given their central role in infection, autoimmunity, and malignancy, dendritic cell deficiency or dysfunction would be expected to have clinical consequences...
October 17, 2016: Current Opinion in Allergy and Clinical Immunology
Cees van Kooten, Ton J Rabelink, Johan W de Fijter, Marlies E J Reinders
PURPOSE OF REVIEW: Progress in the improvement of short-term and long-term outcomes of kidney transplantation seems to have reached a plateau, partially due to consequences of very efficient, but nonspecific immunosuppressive drugs. In recent years, various forms of cell therapy, including the use of mesenchymal stromal cells, have been put forward as an alternative strategy for more defined therapy. It is thought that these therapies will not only allow controlled tapering of immunosuppressive medication, but might bring us also closer to the ambition of generating donor-specific immune regulation and tolerance...
October 15, 2016: Current Opinion in Organ Transplantation
Alice Gutjahr, Capucine Phelip, Anne-Line Coolen, Claire Monge, Anne-Sophie Boisgard, Stéphane Paul, Bernard Verrier
Vaccines have successfully eradicated a large number of diseases. However, some infectious diseases (such as HIV, Chlamydia trachomatis or Bacillus anthracis) keep spreading since there is no vaccine to prevent them. One way to overcome this issue is the development of new adjuvant formulations which are able to induce the appropriate immune response without sacrificing safety. Lymph nodes are the site of lymphocyte priming by antigen-presenting cells and subsequent adaptive immune response, and are a promising target for vaccine formulations...
October 12, 2016: Vaccines
Dawid Walas, Karol Nowicki-Osuch, Dominic Alibhai, Julian Paton
OBJECTIVE: Cerebrovascular remodeling in the SHR may be causative to the known brainstem hypoperfusion. Using RNA sequencing, we examined age-related processes that may govern remodeling of the cerebral arteries in the SHR. DESIGN AND METHOD: In SHR and their progenitor (normotensive) control (Wistar Kyoto, WKY), RNA-seq was performed at three ages: 5, 9, 13 weeks old. Cerebral arteries were flushed and peeled off the brain, stripped of meninges, snap frozen and RNA extracted...
September 2016: Journal of Hypertension
Jennifer L Gardell, David C Parker
The delivery of T-cell help to B cells is antigen-specific, MHC-restricted, and CD40L (CD154) dependent. It has been thought that when a T cell recognizes an antigen-presenting B cell, CD40L expressed on the T-cell surface engages with CD40 on the surface of B cells as long as the cells remain conjugated. To study this, we added fluorescently labeled anti-CD40L antibody during overnight incubation of antigen-presenting B cells with antigen-specific T cells. We discovered that CD40L does not remain on the surface of the T cell, but it is transferred to and endocytosed by B cells receiving T-cell help...
October 18, 2016: European Journal of Immunology
Kevin V Chow, Robyn M Sutherland, Yifan Zhan, Andrew M Lew
Dendritic cells (DCs) are professional antigen presenting cells that consist of functionally and phenotypically heterogeneous populations. Monocyte derived dendritic cells (moDCs) are a DC subset that have been attracting increasing interest due to their potent influence on adaptive immune function and their rapid accumulation upon an inflammatory stimulus. Whilst early studies on moDCs mainly addressed infection, their emergence and function in other settings such as autoimmunity and allogeneic organ transplantation are now being increasingly appreciated...
October 17, 2016: Immunology and Cell Biology
Alexander K Andrianov, Alexander Marin, Thomas R Fuerst
Two macromolecular immunoadjuvants - poly[di(carboxylatophenoxy)phosphazene], PCPP and poly[di(carboxylatoethylphenoxy)phosphazene], PCEP have been investigated for their molecular interactions with model and bio-pharmaceutically important proteins in solutions, as well as for their TLR stimulatory effects and pH-dependent membrane disruptive activity in cellular assays. Solution interactions between polyphosphazenes and proteins, including antigens and soluble immune receptor proteins, have been studied using Asymmetric Flow Field Flow Fractionation (AF4) and Dynamic Light Scattering (DLS) at near physiological conditions - phosphate buffered saline, pH 7...
October 17, 2016: Biomacromolecules
Jason M God, Azizul Haque
No abstract text is available yet for this article.
August 2016: Journal of Clinical & Cellular Immunology
Ragnhild Reehorst Lereim, Eystein Oveland, Yichuan Xiao, Øivind Torkildsen, Stig Wergeland, Kjell-Morten Myhr, Shao-Cong Sun, Frode S Berven
The ubiquitin ligase Peli1 has previously been suggested as a potential treatment target in multiple sclerosis. In the multiple sclerosis disease model, experimental autoimmune encephalomyelitis, Peli1 knock-out led to less activated microglia and less inflammation in the central nervous system. Despite being important in microglia, Peli1 expression has also been detected in glial and neuronal cells. In the present study the overall brain proteomes of Peli1 knock-out mice and wild-type mice were compared prior to experimental autoimmune encephalomyelitis induction, at onset of the disease and at disease peak...
September 2016: Journal of Proteomics & Bioinformatics
Melissa Dullaers, Martijn J Schuijs, Monique Willart, Kaat Fierens, Justine Van Moorleghem, Hamida Hammad, Bart N Lambrecht
BACKGROUND: Allergic asthma is a CD4 Th2-lymphocyte driven disease characterized by airway hyper-responsiveness and eosinophilia. B cells can present antigens to CD4 T cells and produce IgE immunoglobulins which arms effector cells, however mouse models are inconclusive whether B cells are necessary for asthma development. OBJECTIVES: To address the role of B cells in a house dust mite (HDM) driven Th2-high asthma mouse model. METHODS: WT and B cell deficient muMT Mice were sensitized and challenged via the airways with HDM extracts...
October 13, 2016: Journal of Allergy and Clinical Immunology
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