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Dongke Yu, Shi-Ying Cai, Albert Mennone, Pamela Vig, James L Boyer
BACKGROUND & AIMS: Cholestatic liver injury is mediated by bile acid induced inflammatory responses. We hypothesized that superior therapeutic effects might be achieved by combining treatments that reduce the bile acid pool size with one that blocks inflammation. METHODS: Bile duct ligated (BDL) rats and Mdr2(Abcb4)-/- mice were treated with all-trans retinoic acid (atRA), a potent inhibitor of bile acid synthesis, 5mg/kg/day by gavage, or Cenicriviroc (CVC), a known antagonist of CCR2 and CCR5, 50mg/kg/day alone or in combination for 14-day and one month, respectively...
January 22, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
L V Visseaux, A D Durlach, S B Barete, M B B Beylot-Barry, N B Bonnet, A F C Chassine, N F Franck, G H Herve, C L Leclec'h, L M Machet, S I O Ingen-Housz-Oro, T P Petrella, B V Vergier, N O Ortonne, F G Grange
BACKGROUND: A distinctive eruption referred to as "insect bite-like reaction", or "eosinophilic dermatosis of hematologic malignancy" has been described during the course of hematological B-cell malignancies (BCM). However, its clinical evolution, histopathological features and pathogenesis remain unclear. OBJECTIVES: To characterize this eruption and to investigate its pathogenesis and relationship with the underlying BCM. METHODS: In this multicenter retrospective study of the French Study Group on Cutaneous Lymphomas, 37 patients with a BCM and a cutaneous eruption consisting in chronic and/or recurrent papules, papulo-vesicles and/or nodules were included...
January 22, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
Marie Eliane Azoury, Lucia Filì, Rami Bechara, Noémie Scornet, Luc de Chaisemartin, Richard J Weaver, Nancy Claude, Bernard Maillere, Paola Parronchi, Delphine Joseph, Marc Pallardy
BACKGROUND: There is in vitro evidence that T-cells from allergic patients react to benzylpenicillin-human serum albumin (BP-HSA) bioconjugates. Our group has recently shown the existence of naïve CD4+ T lymphocytes recognizing BP-HSA in healthy donors. However, BP-haptenated peptides from HSA participating in the immunization of allergic patients have never been identified. The purpose of the present study is to identify immunodominant BP-haptenated peptides from HSA involved in immunization of patients to BP and to refine the frequency calculation of naïve CD4+ T-cells recognizing BP...
January 22, 2018: Allergy
Fábio D R Sgnotto, Marilia G de Oliveira, Aline A L Lira, Amanda H S Inoue, Tiago O Titz, Raquel L Orfali, Luciana Bento-de-Souza, Maria N Sato, Valeria Aoki, Alberto J S Duarte, Jefferson R Victor
INTRODUCTION: Our group recently demonstrated that IgG modulates αβT cell cytokine production during the maturation process in the human thymus. The effects of this modulation are IgG repertoire dependent and can exert a systemic and long-term impact. OBJECTIVE: To investigate whether IgG from atopic dermatitis (AD) patients can modulate cytokine production of infant intrathymic TCD4 and TCD8 cells in vitro. METHODS: Thymic tissues were obtained from newborn children from nonatopic mothers, and thymocytes were cultured for 6 days with purified IgG from AD patients or with intravenous immunoglobulin (IVIG) or mock conditions as controls...
January 22, 2018: International Journal of Dermatology
Mario Leonardo Squadrito, Chiara Cianciaruso, Sarah K Hansen, Michele De Palma
We describe a lentivirus-encoded chimeric receptor, termed extracellular vesicle (EV)-internalizing receptor (EVIR), which enables the selective uptake of cancer-cell-derived EVs by dendritic cells (DCs). The EVIR enhances DC presentation of EV-associated tumor antigens to CD8+ T cells primarily through MHCI recycling and cross-dressing. EVIRs should facilitate exploring the mechanisms and implications of horizontal transfer of tumor antigens to antigen-presenting cells.
January 22, 2018: Nature Methods
Szu-Han Huang, Yanqin Ren, Allison S Thomas, Dora Chan, Stefanie Mueller, Adam R Ward, Shabnum Patel, Catherine M Bollard, Conrad Russell Cruz, Sara Karandish, Ronald Truong, Amanda B Macedo, Alberto Bosque, Colin Kovacs, Erika Benko, Alicja Piechocka-Trocha, Hing Wong, Emily Jeng, Douglas F Nixon, Ya-Chi Ho, Robert F Siliciano, Bruce D Walker, R Brad Jones
The presence of persistent, latent HIV reservoirs in CD4+ T cells obstructs current efforts to cure infection. The so-called kick-and-kill paradigm proposes to purge these reservoirs by combining latency-reversing agents with immune effectors such as cytotoxic T lymphocytes. Support for this approach is largely based on success in latency models, which do not fully reflect the makeup of latent reservoirs in individuals on long-term antiretroviral therapy (ART). Recent studies have shown that CD8+ T cells have the potential to recognize defective proviruses, which comprise the vast majority of all infected cells, and that the proviral landscape can be shaped over time due to in vivo clonal expansion of infected CD4+ T cells...
January 22, 2018: Journal of Clinical Investigation
Sujal Ghosh, Marlene Carmo, Miguel Calero-Garcia, Ida Ricciardelli, Juan Carlos Bustamante Ogando, Michael P Blundell, Axel Schambach, Philip G Ashton-Rickardt, Claire Booth, Stephan Ehl, Kai Lehmberg, Adrian J Thrasher, H Bobby Gaspar
BACKGROUND: Mutations in the PRF1 gene account for up to 58% of familial haemophagocytic lymphohistiocytosis (FHL) syndromes. The resulting defects in effector cell cytotoxicity lead to hypercytokinaemia and hyperactivation with inflammation in various organs. OBJECTIVE: To determine whether autologous gene corrected T cells can restore cytotoxic function, reduce disease activity and prevent haemophagocytic lymphohistiocytosis (HLH) symptoms in in vivo models. METHODS: We developed a gammaretroviral vector to transduce murine CD8-T cells in the prf-/- mouse model...
January 17, 2018: Journal of Allergy and Clinical Immunology
Dong-Qun Liu, Shuai Lu, Ling-Xiao Zhang, Mei Ji, Shu-Ying Liu, Shao-Wei Wang, Rui-Tian Liu
Therapeutic vaccine is a promising approach in cancer therapy. But tumor-associated antigen peptides have weak immunogenicity and cancer patients are often characterized by immunosuppression and tolerance, leading to less efficiency of immunotherapy. We here successfully developed indoleamine 2, 3-dioxygenase (IDO) siRNA nanoparticle-coated and tyrosinase-related protein 2 (Trp2)-displayed recombinant Saccharomyces cerevisiae (YCP). YCPs had positive charges with a diameter of approximately 5μm, resulting in selective phagocytosis by APC cells...
January 17, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Puneet Tyagi, J Anand Subramony
Nanotechnology ushered the field of medicine in to a new era. Miniaturization, increased surface area, and the unique physicochemical properties in the nano dimension were explored for new applications. Pharmaceutical industry picked up the technology and early success came fast for oral drug delivery through improvement in dissolution properties of the active molecules. Many products were launched using the nanocrystal technology on the oral side. Further development of polymeric nanoparticles led to wide spread research of nanocarriers for parenteral delivery...
January 16, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Arnalda Lanfranchi, Vassilios Lougaris, Lucia Dora Notarangelo, Elena Soncini, Marta Comini, Alessandra Beghin, Federica Bolda, Alessandro Montanelli, Luisa Imberti, Fulvio Porta
We describe the case of a child affected by severe combined immunodeficiency (SCID) with adenosine deaminase (ADA) deficiency showing a maternal T-cell engraftment, a finding that has never been reported before. The presence of engrafted maternal T cells was misleading. Although ADA enzymatic levels were suggestive of ADA-SCID, the child did not present the classical signs of ADA deficiency; therefore, the initial diagnosis was of a conventional SCID. However, ADA toxic metabolites and molecular characterization confirmed this diagnosis...
January 16, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Lin-Shu Zeng, Wen-Ting Huang, Tian Qiu, Ling Shan, Lei Guo, Jian-Ming Ying, Ning Lyu, Xiao-Li Feng
Objective: To investigate the correlation between the clinicopathological features and prognosis in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTCL). Methods: One hundred and four patients diagnosed with ENKTCL at the Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China from November 1991 to September 2011 were included in the study. The clinicopathological features and their correlations with disease prognosis were evaluated in these patients...
December 2017: Chronic Diseases and Translational Medicine
Jun-Xuan Lv, Qi Kong, Xin Ma
Atherosclerosis (AS) is a systemic chronic disease affecting both the coronary and cerebral arteries. Inflammation plays a key role in the initiation and progression of AS, and numerous inflammatory factors have been proposed as potential biomarkers. This article reviews recent research in studies on major circulating inflammatory biomarkers to identify surrogates that may reflect processes associated with AS development and the risk of AS-related vascular events, such as Von Willebrand factor, lectin-like oxidized low-density-lipoprotein receptor-1, soluble urokinase plasminogen activator receptor, regulated upon activation, normal T-cell expressed and secreted, and microparticles, which may provide new perspectives for clinical AS evaluation and risk stratification...
December 2017: Chronic Diseases and Translational Medicine
Augustus M Kilgore, Seth Welsh, Elizabeth E Cheney, Alisha Chitrakar, Trevor J Blain, Benjamin J Kedl, Chris A Hunter, Nathan D Pennock, Ross M Kedl
It is well accepted that the innate response is a necessary prerequisite to the formation of the adaptive response. This is true for T cell responses against infections or adjuvanted subunit vaccination. However, specific innate parameters with predictive value for the magnitude of an adjuvant-elicited T cell response have yet to be identified. We previously reported how T cell responses induced by subunit vaccination were dependent on the cytokine IL-27. These findings were unexpected, given that T cell responses to an infection typically increase in the absence of IL-27...
January 1, 2018: ImmunoHorizons
Friedrich-Carl von Rundstedt, Andrea Necchi
Immunotherapy in urothelial cancer is a quickly evolving field as new agents are being investigated in multiple clinical trials and various clinical settings. The purpose of this review is to provide an insight into the mechanism of these treatments, potential targets to evaluate treatment response and to give an update on the current status of clinical trials. Urothelial cancer is a polyclonal disease with a substantial tumor heterogeneity and a high mutational load which may be beneficial as this may trigger a stronger T-cell mediated immune response...
December 2017: Translational Andrology and Urology
Małgorzata Stosio, Jakub Ruszkowski, Anna Mikosik-Roczyńska, Ireneusz Haponiuk, Jacek M Witkowski
The thymus plays an important role in the development of the immune cell pool; it serves as the primary location for T-lymphocyte maturation. Early cardiac surgical interventions for congenital heart defects are necessarily associated with thymectomy, i.e. the partial or complete removal of the thymus. A newborn infant already has a functioning thymus and developed cells of the immune system. However, thymectomy eliminates the primary location where T cells differentiate and mature. This study summarizes the current knowledge of the cellular disturbances and potential clinical consequences associated with performing thymectomy in children treated surgically for congenital heart defects...
December 2017: Kardiochirurgia i Torakochirurgia Polska, Polish Journal of Cardio-Thoracic Surgery
Ryosuke Sumi, Ariko Miyake, Taiji Endo, Yoshiharu Ohsato, Minh Ha Ngo, Kazuo Nishigaki
Feline lymphomas are associated with the transduction and activation of cellular proto-oncogenes, such as c-myc, by feline leukemia virus (FeLV). We describe a polymerase chain reaction assay for detection of myc transduction usable in clinical diagnosis. The assay targets c-myc exons 2 and 3, which together result in a FeLV-specific fusion gene following c-myc transduction. When this assay was conducted on FeLV-infected feline tissues submitted for clinical diagnosis of tumors, myc transduction was detected in 14% of T-cell lymphoma/leukemias...
January 20, 2018: Archives of Virology
Yan Zhang, Xiuge Wang, Qiang Jiang, Haisheng Hao, Zhihua Ju, Chunhong Yang, Yan Sun, Changfa Wang, Jifeng Zhong, Jinming Huang, Huabin Zhu
Interleukin-6 receptor-alpha (IL6R) interacts with IL6 and forms a ligand-receptor complex, which can stimulate various cellular responses, such as cell proliferation, cell differentiation, and activation of inflammatory processes. Both genetic mutation and epigenetic modification regulate gene transcription. We identified a novel splice variant of bovine IL6R, designated as IL6R-TV, which is characterized by the skipping of exon 2 of the NCBI-referenced IL6R gene (IL6R-reference). The expression levels of IL6R-TV and IL6R-reference transcripts were lower in normal mammary gland tissues...
January 20, 2018: Cell Stress & Chaperones
Yvette L Kasamon, Ephraim J Fuchs, Marianna Zahurak, Gary L Rosner, Heather J Symons, Douglas E Gladstone, Carol Ann Huff, Lode J Swinnen, Robert A Brodsky, William H Matsui, Ivan Borrello, Satish Shanbhag, Kenneth R Cooke, Richard F Ambinder, Leo Luznik, Javier Bolaños-Meade, Richard J Jones
With posttransplantation cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis, nonmyeloablative HLA-haploidentical (NMA haplo) and HLA-matched blood or marrow transplantation (BMT) have comparable outcomes. Early discontinuation of immunosuppression may reduce relapse, as well as improve immune reconstitution, but may increase GVHD. We conducted a prospective trial of NMA haplo BMT for patients with hematologic malignancies (median age, 61), evaluating the safety of early discontinuation of tacrolimus...
January 15, 2018: Biology of Blood and Marrow Transplantation
Raquel López-Mejías, Santos Castañeda, Fernanda Genre, Sara Remuzgo-Martínez, F David Carmona, Javier Llorca, Ricardo Blanco, Javier Martín, Miguel A González-Gay
Immunoglobulin-A vasculitis (IgAV) is classically a childhood small-sized blood vessel vasculitis with predominant involvement of the skin. Gastrointestinal and joint manifestations are common in patients diagnosed with this condition. Nephritis, which is more severe in adults, constitutes the most feared complication of this vasculitis. The molecular bases underlying the origin of IgAV have not been completely elucidated. Nevertheless, several pieces of evidence support the claim that genes play a crucial role in the pathogenesis of this disease...
January 15, 2018: Autoimmunity Reviews
Lina Quan, Xiuwen Lan, Yuanyuan Meng, Xiuchen Guo, Yiwei Guo, Lina Zhao, Xue Chen, Aichun Liu
Immunotherapy has shown encouraging results in lymphoma. Pre-clinical and clinical trials have proven checkpoint blockade, such as PD-1 antibody, as an effective treatment for lymphoma, including diffuse large B-cell lymphoma (DLBCL). Combination of checkpoint blockades has emerged as a new way to treat lymphoma, however, the status of checkpoints expression and their function in DLBCL has not been fully elucidated yet. In this study, we examined the expression of BTLA, PD-1, TIM-3, LIGHT and LAG-3 in tumor micro-environmental T cells of DLBCL using flow cytometry, and compared the cytotoxicity and differentiation status of BTLA+ and BTLA- T-cells...
January 15, 2018: Experimental Hematology
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