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Satyanarayana Swamy Cheekatla, Deepak Tripathi, Sambasivan Venkatasubramanian, Pavan Kumar Nathella, Padmaja Paidipally, Munenori Ishibashi, Elwyn Welch, Amy R Tvinnereim, Mitsuo Ikebe, Vijaya Lakshmi Valluri, Subash Babu, Hardy Kornfeld, Ramakrishna Vankayalapati
In this study, we developed a mouse model of type 2 diabetes mellitus (T2DM) using streptozotocin and nicotinamide and identified factors that increase susceptibility of T2DM mice to infection by Mycobacterium tuberculosis (Mtb). All Mtb-infected T2DM mice and 40% of uninfected T2DM mice died within 10 months, whereas all control mice survived. In Mtb-infected mice, T2DM increased the bacterial burden and pro- and anti-inflammatory cytokine and chemokine production in the lungs relative to those in uninfected T2DM mice and infected control mice...
October 2016: PLoS Pathogens
Christina M Mariaselvam, Ryad Tamouza, Rajagopal Krishnamoorthy, Dominique Charron, Durga Prasanna Misra, Vikramraj K Jain, Vir Singh Negi
INTRODUCTION: NKG2D (KLRK1) is a C-type lectin receptor present on NK cells, γδ, CD8(+) and CD4(+) T cells. Upon ligand binding, NKG2D mediates activatory and co-stimulatory signals to NK cells and activated CD4+ T cells, respectively. Polymorphisms in NKG2D predispose to infectious diseases, cancer, transplantation and autoimmune disorders. We studied the influence of this NK receptor polymorphism on predisposition to and modification of the disease phenotype in patients with Rheumatoid Arthritis (RA)...
October 26, 2016: Clinical and Experimental Immunology
Miljana Radenkovic, Kristina Uvebrant, Oskar Skog, Luis Sarmiento, Jeanette Avartsson, Peter Storm, Petter Vickman, Per-Anders Bertilsson, Malin Fex, Olle Korsgren, Corrado M Cilio
The current view of type 1 diabetes (T1D) is that it is an immune-mediated disease where lymphocytes infiltrate the pancreatic islets, promote killing of beta cells and cause overt diabetes. Although tissue resident immune cells have been demonstrated in several organs, the composition of lymphocytes in human healthy pancreatic islets have been scarcely studied. Here we aimed to investigate the phenotype of immune cells associated to human islets of non-diabetic organ donors. A flow cytometry analysis of isolated islets from perfused pancreases (n=38) was employed to identify alpha, beta, T, NK and B cells...
October 26, 2016: Clinical and Experimental Immunology
Paola Triggianese, Paola Conigliaro, Maria Sole Chimenti, Livia Biancone, Giovanni Monteleone, Roberto Perricone, Ivan Monteleone
OBJECTIVES: Both the innate and the adaptive immune responses contribute to the onset of chronic inflammation in spondyloarthritis (SpA). The association between SpA and inflammatory bowel disease (IBD, enteropathic SpA-ESpA) has been largely established and suggests a shared pathophysiology. There is evidence that innate lymphoid cells (ILC) are involved in the pathogenesis of both SpA and IBD while no evidence has been reported to date on ESpA. We aimed to analyse for the first time the frequency and cytokine expression of ILC in peripheral blood from ESpA patients compared with both IBD and healthy subjects...
October 21, 2016: Clinical and Experimental Rheumatology
Paolo Lissoni
Despite its apparent failure in cancer therapy, IL-2 still remains fundamental in the activation of antitumor immunity. Areas covered: The aim of this review is the reinterpretation of the role of IL-2 in anticancer immunity, according to knowledge gained of the cytokine network, by highlighting its importance in inducing T helper-1 (TH1) cell proliferation, natural killer (NK) actHivation and IL-12 secretion. However, its main negative effect is the stimulation of regulatory T cells (Tregs), which in contrast suppresses anticancer immunity...
October 26, 2016: Expert Review of Clinical Immunology
Yu-Han Meng, Xiao-Hui Zhu, Li-Ying Yan, Yan Zhang, Hong-Yan Jin, Xi Xia, Rong Li, Jie Qiao
INTRODUCTION: The successful pregnancy depends on maternal immune tolerance against the fetus. It has been reported that MSCs (mesenchymal stem cells) could play a regulatory role on immune cells such as CD4(+)T cells, macrophages and NK cells, but their effect on recurrent miscarriage is unknown. STUDY DESIGN: In a prospective study, the abortion-prone (CBA/J × DBA/2) H-2(d) × H-2(k) mice were utilized. Female CBA/J mice (8-10 weeks old) were injected with vehicle or MSCs via tail vein or uterine horns, and 14 days later, they were mated with DBA/2 males for the following experiments...
November 2016: Placenta
Vivien Béziat, Hugo Hilton, Paul J Norman, James A Traherne
Killer-cell immunoglobulin-like receptors (KIRs) are components of two fundamental biological systems essential for human health and survival. Firstly, they contribute to host immune response, both innate and adaptive, through their expression by natural killer (NK) cells and T cells. Secondly, KIR play a key role in regulating placentation, and hence reproductive success. Analogous to the diversity of their HLA class I ligands, KIR are extremely polymorphic. In this review, we describe recent developments, fuelled by methodological advances, which are helping to decipher the KIR system in terms of haplotypes, polymorphisms, expression patterns and their ligand interactions...
October 25, 2016: Immunology
Bradley M Haverkos, Zenggang Pan, Alejandro A Gru, Aharon G Freud, Rachel Rabinovitch, Meng Xu-Welliver, Brad Otto, Carlos Barrionuevo, Robert A Baiocchi, Rosemary Rochford, Pierluigi Porcu
PURPOSE OF REVIEW: Extranodal NK/T cell lymphoma, nasal type (ENKTL-NT) is an aggressive extranodal non-Hodgkin lymphoma most commonly occurring in East Asia and Latin America but with increasing incidence in the United States. Data on epidemiology, disease presentation, and outcome for European and North American ("Western") cases are very limited. We review published landmark clinical studies on ENKTL-NT in the West and report in detail recent data, including our institutional experience...
October 24, 2016: Current Hematologic Malignancy Reports
Rajarsi Mandal, Yasin Şenbabaoğlu, Alexis Desrichard, Jonathan J Havel, Martin G Dalin, Nadeem Riaz, Ken-Wing Lee, Ian Ganly, A Ari Hakimi, Timothy A Chan, Luc G T Morris
Recent clinical trials have demonstrated a clear survival advantage in advanced head and neck squamous cell carcinoma (HNSCC) patients treated with immune checkpoint blockade. These emerging results reveal that HNSCC is one of the most promising frontiers for immunotherapy research. However, further progress in head and neck immuno-oncology will require a detailed understanding of the immune infiltrative landscape found in these tumors. We leveraged transcriptome data from 280 tumors profiled by The Cancer Genome Atlas (TCGA) to comprehensively characterize the immune landscape of HNSCC in order to develop a rationale for immunotherapeutic strategies in HNSCC and guide clinical investigation...
October 20, 2016: JCI Insight
Johan Mj Van den Bergh, Eva Lion, Viggo Fi Van Tendeloo, Evelien Ljm Smits
Interleukin (IL)-15 as a stand-alone therapy can activate the antitumor functions of immune effector cells resulting in significant tumor regression. Interestingly, combining IL-15 with the α-moiety of its receptor (IL-15Rα), also called IL-15 transpresentation, increases the in vivo half-life of IL-15 and enhances binding of IL-15 with cells expressing the IL-15Rβγ, such as NK cells and CD8(+) T cells. These features enlarge the signal transmission of IL-15, resulting in improved proliferation and antitumor activities of both NK cells and CD8(+) T cells, eventually leading to enhanced killing of tumor cells...
October 21, 2016: Pharmacology & Therapeutics
Elisabeth Salzer, Deniz Cagdas, Miroslav Hons, Emily M Mace, Wojciech Garncarz, Özlem Yüce Petronczki, René Platzer, Laurène Pfajfer, Ivan Bilic, Sol A Ban, Katharina L Willmann, Malini Mukherjee, Verena Supper, Hsiang Ting Hsu, Pinaki P Banerjee, Papiya Sinha, Fabienne McClanahan, Gerhard J Zlabinger, Winfried F Pickl, John G Gribben, Hannes Stockinger, Keiryn L Bennett, Johannes B Huppa, Loïc Dupré, Özden Sanal, Ulrich Jäger, Michael Sixt, Ilhan Tezcan, Jordan S Orange, Kaan Boztug
RASGRP1 is an important guanine nucleotide exchange factor and activator of the RAS-MAPK pathway following T cell antigen receptor (TCR) signaling. The consequences of RASGRP1 mutations in humans are unknown. In a patient with recurrent bacterial and viral infections, born to healthy consanguineous parents, we used homozygosity mapping and exome sequencing to identify a biallelic stop-gain variant in RASGRP1. This variant segregated perfectly with the disease and has not been reported in genetic databases. RASGRP1 deficiency was associated in T cells and B cells with decreased phosphorylation of the extracellular-signal-regulated serine kinase ERK, which was restored following expression of wild-type RASGRP1...
October 24, 2016: Nature Immunology
Bethany L Mundy-Bosse, Steven D Scoville, Li Chen, Kathleen McConnell, Hsiaoyin C Mao, Elshafa H Ahmed, Nicholas Zorko, Sophia Harvey, Jordan Cole, Xiaoli Zhang, Stefan Costinean, Carlo M Croce, Karilyn Larkin, John C Byrd, Sumithira Vasu, William Blum, Jianhua Yu, Aharon G Freud, Michael A Caligiuri
Natural killer (NK) cells can have potent antileukemic activity following haplo-mismatched, T cell-depleted stem cell transplantations for the treatment of acute myeloid leukemia (AML), but they are not successful in eradicating de novo AML. Here, we have used a mouse model of de novo AML to elucidate the mechanisms by which AML evades NK cell surveillance. NK cells in leukemic mice displayed a marked reduction in the cytolytic granules perforin and granzyme B. Further, as AML progressed, we noted the selective loss of an immature subset of NK cells in leukemic mice and in AML patients...
October 24, 2016: Journal of Clinical Investigation
Yajuan Qiu, Zhiyuan Zhou, Zhaoming Li, Lisha Lu, Ling Li, Xin Li, Xinhua Wang, Mingzhi Zhang
PURPOSE: The aim of the present study was to identify the potential relevant biomarkers to predict the therapeutic response of advanced extranodal NK/T cell lymphoma(ENKTL) treated with asparaginase-based treatment. EXPERIMENTAL DESIGN: We used proteomic technology to identify differentially expressed proteins between chemotherapy-resistant and chemotherapy-sensitive patients. Then we used enzyme-linked immunosorbent assay to validate the predictive value of selective biomarkers...
October 24, 2016: Proteomics. Clinical Applications
Silvia Pesce, Lorenzo Moretta, Alessandro Moretta, Emanuela Marcenaro
Innate and adaptive immunity has evolved complex molecular mechanisms regulating immune cell migration to facilitate the dynamic cellular interactions required for its function involving the chemokines and their receptors. One important chemokine receptor in the immune system is represented by CCR7. Together with its ligands CCL19 and CCL21, this chemokine receptor controls different arrays of migratory events, both in innate and adaptive immunity, including homing of CD56(bright) NK cells, T cells, and DCs to lymphoid compartments, where T cell priming occurs...
2016: Frontiers in Immunology
Jena D French, Keith Bible, Christine Spitzweg, Bryan R Haugen, Mabel Ryder
Inflammation has long been associated with the thyroid and with thyroid cancers, raising seminal questions about the role of the immune system in the pathogenesis of advanced thyroid cancers. With a growing understanding of dynamic tumour-immune cell interactions and the mechanisms by which tumour cells evade antitumour immunity, the field of cancer immunotherapy has been revolutionised. In this Review, we provide evidence to support the presence of an antitumour immune response in advanced thyroid cancers linked to cytotoxic T cells and NK cells...
October 20, 2016: Lancet Diabetes & Endocrinology
Agnes S Harahap, Stephanie Marisca, Maria F Ham, Endang S R Hardjolukito
No abstract text is available yet for this article.
February 2016: Pathology
Chandra Bura, Shaun Chou, Winny Varikatt
No abstract text is available yet for this article.
February 2016: Pathology
Marek Sierzega, Marzena Lenart, Magdalena Rutkowska, Marta Surman, Bozenna Mytar, Andrzej Matyja, Maciej Siedlar, Jan Kulig
BACKGROUND: Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR) may serve as a simple index of the immune function. The aim of this study was to investigate the prognostic significance of NLR, PLR, and LMR in patients with resectable pancreatic ductal adenocarcinoma (PDAC) and to verify whether such biomarkers are associated with changes in populations of lymphoid cells. METHODS: The prognostic implications of blood count parameters were evaluated in a retrospective cohort of 442 subjects undergoing pancreatic resections for PDAC...
October 21, 2016: Annals of Surgical Oncology
Catharina C Gross, Diana Ahmetspahic, Tobias Ruck, Andreas Schulte-Mecklenbeck, Kathrin Schwarte, Silke Jörgens, Stefanie Scheu, Susanne Windhagen, Bettina Graefe, Nico Melzer, Luisa Klotz, Volker Arolt, Heinz Wiendl, Sven G Meuth, Judith Alferink
OBJECTIVE: To characterize changes in myeloid and lymphoid innate immune cells in patients with relapsing-remitting multiple sclerosis (MS) during a 6-month follow-up after alemtuzumab treatment. METHODS: Circulating innate immune cells including myeloid cells and innate lymphoid cells (ILCs) were analyzed before and 6 and 12 months after onset of alemtuzumab treatment. Furthermore, a potential effect on granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-23 production by myeloid cells and natural killer (NK) cell cytolytic activity was determined...
December 2016: Neurology® Neuroimmunology & Neuroinflammation
Takeshi Kimura, Akihiro Yamashita, Keiichi Ozono, Noriyuki Tsumaki
Articular cartilage damage does not spontaneously heal and could ultimately result in a loss of joint function. Damaged cartilage can be repaired with cell/tissue sources that are transplanted, however, autologous chondrocytes are limited in number as a cell source. Induced pluripotent stem cells (iPSCs) are a relatively new and abundant cell source and can be made from the patient, but at considerable cost. Because cartilage is immunoprivileged tissue, allogeneic cartilages have been transplanted effectively without matching for human leukocyte antigen (HLA), but are difficult to acquire due to scarcity of donors...
October 20, 2016: Tissue Engineering. Part A
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