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Immunity, Inflammation and Disease

Marion Depla, Sandy Pelletier, Nathalie Bédard, Camille Brunaud, Julie Bruneau, Naglaa H Shoukry
INTRODUCTION: Polymorphisms in the type III interferon IFN-λ3 and the killer cell immunoglobulin-like receptor (KIR) genes controlling the activity of natural killer (NK) cells can predict spontaneous resolution of acute hepatitis C virus (HCV) infection. We hypothesized that IFN-λ3 polymorphism may modulate NK cell function during acute HCV. METHODS: We monitored the plasma levels of type III IFNs in relation to the phenotype and the function of NK cells in a cohort of people who inject drugs (PWID) during acute HCV infection with different outcomes...
September 2016: Immunity, Inflammation and Disease
Pragya Yadav, Matthew T Carr, Ruby Yu, Alice Mumbey-Wafula, Linda A Spatz
INTRODUCTION: The Epstein Barr Virus (EBV) has been associated with the autoimmune disease, Systemic Lupus Erythematosus (SLE). EBV nuclear antigen-I (EBNA-1) is the major nuclear protein of EBV. We previously generated an IgG monoclonal antibody (MAb) to EBNA-1, 3D4, and demonstrated that it cross-reacts with double stranded DNA (dsDNA) and binds the 148 amino acid viral binding site (VBS) in the carboxyl region of EBNA-1. The aim of the present study was to characterize another antibody to EBNA-1 that cross-reacts with dsDNA, compare its immunoglobulin genes to 3D4, and finely map the epitope in EBNA-1 that is recognized by these cross-reactive antibodies...
September 2016: Immunity, Inflammation and Disease
Muriel Smet, Lien Van Hoecke, Ans De Beuckelaer, Seppe Vander Beken, Thomas Naessens, Karl Vergote, Monique Willart, Bart N Lambrecht, Jan-Åke Gustafsson, Knut R Steffensen, Johan Grooten
INTRODUCTION: Liver X receptors (LXRs) are nuclear receptors that function as cholesterol sensors and regulate cholesterol homeostasis. High cholesterol has been recognized as a risk factor in asthma; however, the mechanism of this linkage is not known. METHODS: To explore the importance of cholesterol homeostasis for asthma, we investigated the contribution of LXR activity in an ovalbumin- and a house dust mite-driven eosinophilic asthma mouse model. RESULTS: In both models, airway inflammation, airway hyper-reactivity, and goblet cell hyperplasia were reduced in mice deficient for both LXRα and LXRβ isoforms (LXRα(-/-)β(-/-)) as compared to wild-type mice...
September 2016: Immunity, Inflammation and Disease
Yosuke Kanno, Akira Ishisaki, Mei Miyashita, Osamu Matsuo
INTRODUCTION: Chronic inflammatory diseases, such as rheumatoid arthritis and periodontitis, cause the bone destruction by promotion of the differentiation of monocyte/macrophage lineage cells into mature osteoclasts (OCs) with active bone-resorbing character. However, the detailed mechanisms underlying this disorder remain unclear. We herein investigated the role of urokinase plasminogen activator receptor (uPAR) in the bone destruction caused by chronic inflammation. METHODS: We investigated that the effect of uPAR on inflammatory OC formation induced by lipopolysaccharide (LPS) in inflammatory diseases...
September 2016: Immunity, Inflammation and Disease
Siv H Moen, Marita Westhrin, Muhammad Zahoor, Nikolai N Nørgaard, Hanne Hella, Berit Størdal, Anders Sundan, Nadra J Nilsen, Anne-Marit Sponaas, Therese Standal
INTRODUCTION: Mesenchymal stem cells, also called mesenchymal stromal cells, MSCs, have great potential in stem cell therapy partly due to their immunosuppressive properties. How these cells respond to chronic inflammatory stimuli is therefore of importance. Toll-like receptors (TLR)s are innate immune receptors that mediate inflammatory signals in response to infection, stress, and damage. Caspase-8 is involved in activation of NF-kB downstream of TLRs in immune cells. Here we investigated the role of caspase-8 in regulating TLR-induced cytokine production from human bone marrow-derived mesenchymal stromal cells (hBMSCs)...
September 2016: Immunity, Inflammation and Disease
Yeneneh Haileselassie, Marit Navis, Nam Vu, Khaleda Rahman Qazi, Bence Rethi, Eva Sverremark-Ekström
INTRODUCTION: In early-life, the immature mucosal barrier allows contact between the gut microbiota and the developing immune system. Due to their strategic location and their ability to sample luminal antigen, dendritic cells (DC) play a central role in the interaction of microbes and immune cells in the gut. Here, we investigated how two bacteria associated with opposite immune profiles in children, that is, Lactobacillus (L.) reuteri and Staphylococcus (S.) aureus, influenced the differentiation of monocytes in vitro as well how the generated DC impacted T cell responses...
September 2016: Immunity, Inflammation and Disease
Tarcio Teodoro Braga, Matheus Correa-Costa, Hatylas Azevedo, Reinaldo Correia Silva, Mario Costa Cruz, Maira Estanislau Soares Almeida, Meire Ioshie Hiyane, Carlos Alberto Moreira-Filho, Marinilce Fagundes Santos, Katia Regina Perez, Iolanda Midea Cuccovia, Niels Olsen Saraiva Camara
INTRODUCTION: Macrophages are heterogeneous and thus can be correlated with distinct tissue outcomes after injury. Conflicting data have indicated that the M2-related phenotype directly triggers fibrosis. Conversely, we hypothesize here that the inflammatory milieu provided by early infiltration of pro-inflammatory macrophages dictates tissue scarring after injury. METHODS AND RESULTS: We first determined that tissue-localized macrophages exhibit a pro-inflammatory phenotype (p40IL12(+)CCR7(+)CD11b(+)) during the early phase of a chronic injury model, in contrast to a pro-resolving phenotype (Arg1(+)IL10(+)CD206(+)CD11b(+)) at a later stage...
September 2016: Immunity, Inflammation and Disease
Lydie Cassard, Ana Inés Lalanne, Peggy Garault, Aurélie Cotillard, Christian Chervaux, Michiel Wels, Tamara Smokvina, Marc Daëron, Raphaëlle Bourdet-Sicard
INTRODUCTION: The microbiota controls a variety of biological functions, including immunity, and alterations of the microbiota in early life are associated with a higher risk of developing allergies later in life. Several probiotic bacteria, and particularly lactic acid bacteria, were described to reduce both the induction of allergic responses and allergic manifestations. Although specific probiotic strains were used in these studies, their protective effects on allergic responses also might be common for all lactobacilli...
September 2016: Immunity, Inflammation and Disease
JoAnn Trial, Katarzyna A Cieslik, Mark L Entman
INTRODUCTION: We studied monocyte transendothelial migration and subsequent polarization into M1/M2 macrophages in response to C-reactive protein (CRP) with two disease-related ligands: (1) phosphocholine (PC) and (2) multilamellar liposomes containing both unoxidized and oxidized forms of the lipid, phosphatidylcholine. These ligands differ in biological origin: PC is present on bacterial cell walls while oxidized lipids are present in atherogenic lipids. METHODS: We used an in vitro model of human monocyte transendothelial migration and assessed the polarization of monocytes and T cells and signaling through Fcγ receptors in monocytes...
September 2016: Immunity, Inflammation and Disease
Yuya Yoshida, Norihisa Mikami, Yuki Matsushima, Mai Miyawaki, Hiroki Endo, Rie Banno, Takumi Tsuji, Tetsuro Fujita, Takeyuki Kohno
INTRODUCTION: Combination treatment with fingolimod (FTY720) plus pathogenic antigen is thought to prevent glucose-6-phosphate isomerase (GPI)325-339-induced arthritis progression by effective induction of immune tolerance. Here, we examined the efficacy of this combination treatment on remission maintenance. METHODS: GPI325-339-induced arthritis mice were treated for 5 days with FTY720 (1.0 mg/kg, p.o.) alone, GPI325-339 (10 μg/mouse, i.v.) alone, or with the FTY720 plus GPI325-339 combination...
September 2016: Immunity, Inflammation and Disease
Ramakrishna Edukulla, Kira Lee Rehn, Bo Liu, Jaclyn W McAlees, Gurjit K Hershey, Yui Hsi Wang, Ian Lewkowich, Andrew W Lindsley
INTRODUCTION: Ceramide is the central substrate of sphingolipid metabolism and plays a key role in cellular signal transduction pathways, regulating apoptosis, differentiation, and chemotaxis. Alterations in airway ceramide levels are observed in multiple pulmonary diseases and recent human genetic association studies have linked dysregulation of sphingolipid regulatory genes with asthma pathogenesis. METHODS: Utilizing myriocin, a potent inhibitor of sphingolipid synthesis, we evaluated the immune regulatory role of de novo ceramide generation in vitro and in vivo...
September 2016: Immunity, Inflammation and Disease
Theresa M Leichner, Atsushi Satake, Taku Kambayashi
To maintain immune tolerance, regulatory T cell (Treg) numbers must be closely indexed to the number of conventional T cells (Tconvs) so that an adequate Treg:Tconv ratio can be maintained. Two factors important in this process are the cytokine interleukin-2 (IL-2) and T cell receptor (TCR) stimulation by major histocompatibility complex class II (MHC-II). Here, we report that in addition to TCR stimulation of Tregs themselves, the maintenance of Tregs also requires TCR signaling by Tconvs. We found that Tconvs produce IL-2 in response to self-peptide-MHC-II complexes and that Tconvs possessing more highly self-reactive TCRs express more IL-2 at baseline...
June 2016: Immunity, Inflammation and Disease
Ryo Atomura, Terukazu Sanui, Takao Fukuda, Urara Tanaka, Kyosuke Toyoda, Takaharu Taketomi, Kensuke Yamamichi, Hajime Akiyama, Fusanori Nishimura
Periodontitis is a chronic inflammatory disorder caused by specific bacteria residing in the biofilm, particularly Porphyromonas gingivalis (Pg). Sprouty2 (Spry2) functions as a negative regulator of the fibroblast growth factor (FGF) signaling pathway. We previously demonstrated that sequestration of Spry2 induced proliferation and osteogenesis in osteoblastic cells by basic FGF (bFGF) and epidermal growth factor (EGF) stimulation in vitro, but diminished cell proliferation in gingival epithelial cells. In addition, Spry2 knockdown in combination with bFGF and EGF stimulation increases periodontal ligament cell proliferation and migration accompanied by prevention of osteoblastic differentiation...
March 2016: Immunity, Inflammation and Disease
Matthew P Spindler, Alvin M Ho, David Tridgell, Marli McCulloch-Olson, Vivian Gersuk, Chester Ni, Carla Greenbaum, Srinath Sanda
Normal glucose metabolism is critical to immune function but the effects of short-term hyperglycemia on immunity are not well described. To study this phenomenon, we induced hyperglycemia in healthy subjects for 2 h with intravenous dextrose and octreotide. An RNA-seq analysis of whole blood RNA demonstrated alterations in multiple immune pathways and transcripts during acute hyperglycemia including decreased transcription of IL-6, an important component of both innate and adaptive immune responses. Additional in vitro studies of human peripheral blood mononuclear cells (PBMCs) exposed to high glucose confirmed decreased IL-6 expression, most prominently in CD14(+)CD16(+) intermediate monocytes...
March 2016: Immunity, Inflammation and Disease
Sujani Kakumanu, Katy Jaffee, Cynthia M Visness, Amy Dresen, Melissa Burger, Frank R Witter, George T O'Connor, William W Cruikshank, Wayne G Shreffler, Leonard B Bacharier, James E Gern
Asthma in the inner-city population is usually atopic in nature, and is associated with significant morbidity and mortality. However, the underlying immune abnormalities that underlie asthma in urban adults have not been well defined. We investigated the influence of atopy and asthma on cytokine responses of inner-city adult women to define immune abnormalities associated with asthma and atopy. Blood samples were collected from 509 of 606 inner-city women enrolled in the Urban Environment and Childhood Asthma (URECA) study...
March 2016: Immunity, Inflammation and Disease
Kosuke Ohira, Ayako Nakahara, Satoru Konnai, Tomohiro Okagawa, Asami Nishimori, Naoya Maekawa, Ryoyo Ikebuchi, Junko Kohara, Shiro Murata, Kazuhiko Ohashi
CD4(+)CD25(high)Foxp3(+) T cells suppress excess immune responses that lead to autoimmune and/or inflammatory diseases, and maintain host immune homeostasis. However, CD4(+)CD25(high)Foxp3(+) T cells reportedly contribute to disease progression by over suppressing immune responses in some chronic infections. In this study, kinetic and functional analyses of CD4(+)CD25(high)Foxp3(+) T cells were performed in cattle with bovine leukemia virus (BLV) infections, which have reported immunosuppressive characteristics...
March 2016: Immunity, Inflammation and Disease
Ida Waern, Iulia Karlsson, Gunnar Pejler, Sara Wernersson
Mast cells contain large amounts of fully active proteases that are stored in complex with serglycin proteoglycan in their secretory granules. Upon degranulation, such serglycin:protease complexes are released to the extracellular space and can potentially have an impact on the local inflammatory reaction, either through direct effects of serglycin proteoglycan or through effects mediated by its bound proteases. The objective of this study was to address this scenario by investigating the possibility that serglycin-associated proteases can regulate levels of pro-inflammatory cytokines...
March 2016: Immunity, Inflammation and Disease
Catherine Cho, Anna Nguyen, Katherine J Bryant, Sean G O'Neill, H Patrick McNeil
Mast cells (MCs) participate in diseases such as systemic mastocytosis (SM) and allergic conditions. Less well understood is the role of MCs in non-allergic inflammatory disorders like rheumatoid arthritis (RA). Studying definitive roles for MCs in human diseases has been hampered by the lack of a well-accepted biomarker for monitoring in vivo MC activation. This study aimed to investigate the utility of urinary tetranor PGDM (T-PGDM) as a biomarker of in vivo MC activation in patients with SM, and apply this biomarker to assess MC involvement in relation to RA disease activity...
March 2016: Immunity, Inflammation and Disease
Christopher M Royer, Karin Rudolph, Gregory N Dietsch, Robert M Hershberg, Edward G Barrett
VTX-1463 is a selective toll-like receptor (TLR) 8 agonist that activates a subset of innate immune cells to produce a unique cytokine profile. Delivery of VTX-1463 via nasal spray may modulate the nasal response in allergic rhinitis. The aim of this study was to determine the effects of VTX-1463 on the nasal response in a dog model of allergic rhinitis. Ragweed (RW)-sensitized dogs were pretreated with increasing doses of VTX-1463 1 day prior to RW challenge or with two doses (4 or 8 days and 1 day prior to RW)...
March 2016: Immunity, Inflammation and Disease
Direkrit Chiewchengchol, Helen L Wright, Huw B Thomas, Connie W Lam, Kate J Roberts, Nattiya Hirankarn, Michael W Beresford, Robert J Moots, Steven W Edwards
Responses of human neutrophils to TNF-α are complex and multifactorial. Exposure of human neutrophils to TNF-α in vitro primes the respiratory burst, delays apoptosis and induces the expression of several genes including chemokines, and TNF-α itself. This study aimed to determine the impact of TNF-α exposure on the expression of neutrophil genes and proteins that regulate apoptosis. Quantitative PCR and RNA-Seq, identified changes in expression of several apoptosis regulating genes in response to TNF-α exposure...
March 2016: Immunity, Inflammation and Disease
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