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European Journal of Immunology

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https://www.readbyqxmd.com/read/28543188/cd44-deletion-leading-to-attenuation-of-experimental-autoimmune-encephalomyelitis-results-from-alterations-in-gut-microbiome-in-mice
#1
Kumaraswamy Naidu Chitrala, Hongbing Guan, Narendra P Singh, Brandon Busbee, Alexa Gandy, Pegah Mehrpouya-Bahrami, Mitra S Ganewatta, Chuanbing Tang, Saurabh Chatterjee, Prakash Nagarkatti, Mitzi Nagarkatti
Dysbiosis in gut microbiome has been shown to be associated with inflammatory and autoimmune diseases. Previous studies from our laboratory demonstrated the pivotal role played by CD44 in the regulation of experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis. In the current study, we determined whether these effects resulted from an alteration in gut microbiota and the short-chain fatty acid (SCFA) production in CD44KO mice. Fecal transfer from naïve CD44KO but not CD44WT mice, into EAE-induced CD44WT mice, led to significant amelioration of EAE...
May 23, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28508576/mhc-i-presentation-of-toxoplasma-gondii-immunodominant-antigen-does-not-require-sec-22b-and-is-regulated-by-antigen-orientation-at-the-vacuole-membrane
#2
Célia Buaillon, Nestor A Guerrero, Ignacio Cebrian, Sophie Blanié, Jodie Lopez, Emilie Bassot, Virginie Vasseur, Julien Santi-Rocca, Nicolas Blanchard
The intracellular Toxoplasma gondii parasite replicates within a parasitophorous vacuole (PV). T. gondii secretes proteins that remain soluble in the PV space, are inserted into PV membranes or are exported beyond the PV boundary. In addition to supporting T. gondii growth, these proteins can be processed and presented by MHC I for CD8(+) T-cell recognition. Yet it is unclear whether membrane binding influences the processing pathways employed and if topology of membrane antigens impacts their MHC I presentation...
May 15, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28508449/satellite-glial-cells-in-human-trigeminal-ganglia-have-a-broad-expression-of-functional-toll-like-receptors
#3
Johanna G Mitterreiter, Werner J D Ouwendijk, Monique van Velzen, Gijsbert P van Nierop, Albert D M E Osterhaus, Georges M G M Verjans
Toll-like receptors (TLRs) orchestrate immune responses to a wide variety of danger- and pathogen-associated molecular patterns. Compared to the central nervous system (CNS), expression profile and function of TLRs in the human peripheral nervous system (PNS) are ill-defined. We analyzed TLR expression of satellite glial cells (SGCs) and microglia, glial cells predominantly involved in local immune responses in ganglia of the human PNS and normal-appearing white matter (NAWM) of the CNS, respectively. Ex vivo flow cytometry analysis of cell suspensions obtained from human cadaveric trigeminal ganglia (TG) and NAWM showed that both SGCs and microglia expressed TLR1-5, TLR7 and TLR9, although expression levels varied between these cell types...
May 15, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28504304/exploiting-scavenger-receptors-in-cancer-immunotherapy-lessons-from-cd5-and-sr-b1
#4
REVIEW
Marcos Vasquez, Inês Simões, Marta Consuegra-Fernández, Fernando Aranda, Francisco Lozano, Pedro Berraondo
Scavenger receptors (SRs) are structurally heterogeneous cell surface receptors characterized by their capacity to remove extraneous or modified self-macromolecules from circulation, thus avoiding the accumulation of noxious agents in the extracellular space. This scavenging activity makes SRs important molecules for host defense and homeostasis. In turn, SRs keep the activation of the steady state immune response in check, and participate as co-receptors in the priming of the effector immune responses when the macromolecules are associated with a threat that might compromise host homeostasis...
May 15, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28493377/neonatal-myeloid-derived-suppressor-cells-show-reduced-apoptosis-and-immunosuppressive-activity-upon-infection-with-escherichia-coli
#5
Anja Leiber, Julian Schwarz, Natascha Köstlin, Bärbel Spring, Birgit Fehrenbach, Nenad Katava, Christian F Poets, Christian Gille
BACKGROUND: Susceptibility to infection during the neonatal period and reduced control of inflammation in neonates are attributed to immunosuppression persisting from fetal life. Myeloid-derived suppressor cells (MDSCs) are immature myeloid progenitors with suppressive activity and increased numbers in cord blood. We hypothesized that MDSCs contribute to innate host defence in neonates, paralleled by anti-inflammatory signalling. METHODS: Phagocytic activity, infection induced apoptosis, expression of B-cell lymphoma (Bcl)-2 family proteins, production of reactive oxygen species (ROS), cytokine production and T-cell suppression of neonatal granulocytic-MDSCs (G-MDSCs) after infection with Escherichia coli (E...
May 11, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28480512/regulation-of-immune-cell-signaling-by-ship1-a-phosphatase-scaffold-protein-and-potential-therapeutic-target
#6
REVIEW
Samantha D Pauls, Aaron J Marshall
The phosphoinositide phosphatase SHIP is a critical regulator of immune cell activation. Despite considerable study, the mechanisms controlling SHIP activity to ensure balanced cell activation remain incompletely understood. SHIP dampens B-cell antigen receptor (BCR) signaling in part through its association with the inhibitory co-receptor FcγRIIB, and serves as an effector for other inhibitory receptors in various immune cell types. The established paradigm emphasizes SHIP's inhibitory receptor-dependent function in regulating phosphoinositide 3-kinase (PI3K) signaling by dephosphorylating the phosphoinositide PI(3,4,5)P3 ; however, substantial evidence indicates that SHIP can be activated independently of inhibitory receptors and can function as an intrinsic brake on activation signaling...
May 7, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28475283/cd69-from-activation-marker-to-metabolic-gatekeeper
#7
REVIEW
Danay Cibrián, Francisco Sánchez-Madrid
CD69 is a membrane-bound, type II C-lectin receptor. It is a classical early marker of lymphocyte activation due to its rapid appearance on the surface of the plasma membrane after stimulation. CD69 is expressed by several subsets of tissue resident immune cells, including resident memory T (TRM) cells and gamma delta (γδ) T cells, and is therefore considered a marker of tissue retention. Recent evidence has revealed that CD69 regulates some specific functions of selected T-cell subsets, determining the migration-retention ratio as well as the acquisition of effector or regulatory phenotypes...
May 5, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28475279/nk-cells-generate-memory-type-responses-to-human-cytomegalovirus-infected-fibroblasts
#8
Nicholas Newhook, Neva Fudge, Michael Grant
Natural killer (NK) cells are cytotoxic lymphocytes that selectively respond against abnormal cells. Human cytomegalovirus (HCMV) infection causes expansion of NKG2C(+) CD57(+) NK cells in vivo and NKG2C(+) NK cells proliferate when cultured with HCMV-infected cells. This raises the possibility of an NK-cell subset selectively responding against a specific pathogen and accruing memory. To test this possibility, we compared proliferation, natural cytotoxicity and interferon-γ (IFN-γ) production of NK cells from HCMV-seropositive and HCMV-seronegative individuals co-cultured with HCMV-infected or uninfected MRC-5 cells...
May 5, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28471480/microrna-142-controls-thymocyte-proliferation
#9
Alexander Mildner, Elik Chapnik, Diana Varol, Tegest Aychek, Nardi Lampl, Natalia Rivkin, Anita Bringmann, Franziska Paul, Sigalit Boura-Halfon, Yifat Segal Hayoun, Zohar Barnett-Itzhaki, Ido Amit, Eran Hornstein, Steffen Jung
T-cell development is a spatially and temporally regulated process, orchestrated by well-defined contributions of transcription factors and cytokines. Here, we identify the non-coding RNA miR-142 as an additional regulatory layer within murine thymocyte development and proliferation. MiR-142 deficiency impairs the expression of cell cycle-promoting genes in mature mouse thymocytes and early progenitors, accompanied with increased levels of Cyclin-dependent kinase inhibitor 1B (Cdkn1b, also known as p27(Kip1) )...
May 4, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28463395/clinical-relevance-of-circulating-anti-ena-and-anti-dsdna-secreting-cells-from-sle-patients-and-their-dependence-on-stat-3-activation
#10
Raquel de la Varga Martínez, Beatriz Rodríguez-Bayona, Gustavo A Añez, Fermín Medina Varo, José J Pérez Venegas, José A Brieva, Carmen Rodríguez
Disturbances of plasma cell homeostasis and auto-antibody production are hallmarks of systemic lupus erythematosus. The aim of this study was to explore the presence of circulating anti-ENA and anti-dsDNA antibody-secreting cells, to determine their dependence on plasma cell-niche cytokines and to analyze their clinical value. The study was performed in SLE patients with serum anti-ENA and/or anti-dsDNA antibodies (n = 57). Enriched B-cell fractions and sorted antibody-secreting cells (CD19(low) CD38(high) ) were obtained from blood...
May 2, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28444759/dysregulated-cd46-shedding-interferes-with-th1-contraction-in-systemic-lupus-erythematosus
#11
Ursula Ellinghaus, Andrea Cortini, Christopher L Pinder, Gaelle Le Friec, Claudia Kemper, Timothy J Vyse
IFN-γ-producing T helper 1 (Th1) cell responses mediate protection against infections but uncontrolled Th1 activity also contributes to a broad range of autoimmune diseases. Autocrine complement activation has recently emerged as key in the induction and contraction of human Th1 immunity: activation of the complement regulator CD46 and the C3aR expressed by CD4(+) T cells via autocrine generated ligands C3b and C3a, respectively, are critical to IFN-γ production. Further, CD46-mediated signals also induce co-expression of immunosuppressive IL-10 in Th1 cells and transition into a (self)-regulating and contracting phase...
April 26, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28440548/contact-sensitizers-trigger-human-cd1-autoreactive-t-cell-responses
#12
Richard J Betts, Adrijana Perkovic, Subhashree Mahapatra, Aurélia Del Bufalo, Kaddy Camara, Amy R Howell, Silvia Martinozzi Teissier, Gennaro De Libero, Lucia Mori
Allergic contact dermatitis is a primarily T-cell-mediated inflammatory skin disease induced by exposure to small molecular-weight haptens, which covalently bind to proteins. The abundance of cutaneous T cells that recognize CD1a antigen-presenting molecules raises the possibility that MHC-independent antigen presentation may be relevant in some hapten-driven immune responses. Here we examine the ability of contact sensitizers to influence CD1-restricted immunity. Exposure of human antigen-presenting cells such as monocyte-derived dendritic cells and THP-1 cells to the prototypical contact sensitizer dinitrochlorobenzene potentiated the response of CD1a- and CD1d-autoreactive T cells, which released a vast array of cytokines in a CD1- and TCR-dependent manner...
April 25, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28439878/dissecting-and-modeling-the-emergent-murine-tec-compartment-during-ontogeny
#13
Fabian Brunk, Chloé Michel, Tim Holland-Letz, Alla Slynko, Annette Kopp-Schneider, Bruno Kyewski, Sheena Pinto
The origin of the thymic epithelium, i.e. the cortical (cTEC) and medullary (mTEC) epithelial cells, from bipotent stem cells through TEC progenitors and lineage-specific progeny still remains poorly understood. We sought to obtain an unbiased view of the incipient emergence of TEC subsets by following embryonic TEC development based on co-expression of EpCAM, CD80 and MHC class II (MHCII) on non-hematopoietic (CD45(-) ) thymic stromal cells in wild-type BL6 mice. Using a combination of ex vivo analysis, Re-aggregate Thymic Organ Culture (RTOC) reconstitution assays and mathematical modeling, we traced emergent lineage commitment in murine embryonic TECs...
April 25, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28426152/donor-specific-alloreactive-t-cells-can-be-quantified-from-whole-blood-and-may-predict-cellular-rejection-after-renal-transplantation
#14
Michaela Fischer, Sarah Leyking, Marco Schäfer, Julia Elsäßer, Martin Janssen, Janine Mihm, Kai van Bentum, Danilo Fliser, Martina Sester, Urban Sester
Preformed cellular alloreactivity can exist prior to transplantation and may contribute to rejection. Here, we used a rapid flow-cytometric whole-blood assay to characterize the extent of alloreactive T cells among 1491 stimulatory reactions from 61 renal transplant candidates and 75 controls. The role of preformed donor-specific alloreactive T cells in cellular rejection was prospectively analyzed in 21 renal transplant recipients. Alloreactive CD8(+) T cells were more frequent than respective CD4(+) T cells, and these levels were stable over time...
April 20, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28386999/psoriatic-cutaneous-inflammation-promotes-human-monocyte-differentiation-into-active-osteoclasts-facilitating-bone-damage
#15
Annunziata Raimondo, Serena Lembo, Roberta Di Caprio, Giovanna Donnarumma, Giuseppe Monfrecola, Nicola Balato, Fabio Ayala, Anna Balato
Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy that can be associated with focal bone erosions. Psoriasis usually precedes the psoriatic arthritis onset by an average of 10 years, but this relation is not yet fully elucidated. Pro-inflammatory cytokines, such as IL-33, OPN, IL-17, and TNF-α are involved in both psoriasis and PsA pathogenesis as well as in bone homeostasis. In this study, we have demonstrated that IL-33, OPN, IL-17, and TNF-α induced the release of a wide range of pro-osteoclastogenic factors from the skin, such as RANKL, that promote monocyte differentiation in osteoclasts...
April 7, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28386934/eomes-expression-reports-the-progressive-differentiation-of-ifn-%C3%AE-producing-th1-like-%C3%AE-%C3%AE-t%C3%A2-cells
#16
Ciro N R Lino, Joana Barros-Martins, Linda Oberdörfer, Thierry Walzer, Immo Prinz
The transcription factor Eomesodermin (Eomes) plays a crucial role in regulating cytotoxic function, development, and survival of immune cells. γδ T cells can express Eomes, but its contribution to their differentiation is unknown. Using Eomes-IRES-GFP mice, we show that Eomes(+) γδ T cells are unequally distributed among organs, with the highest proportion in spleen. While the majority of Eomes(+) γδ T cells expressed Vγ1(+) and Vγ4(+) TCRs, Eomes was absent in Vγ5(+) , Vγ6(+) , and Vγ7(+) subsets...
April 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28386908/inhibitory-2b4-contributes-to-nk-cell-education-and-immunological-derangements-in-xlp1-patients
#17
Raffaella Meazza, Michela Falco, Stefania Marcenaro, Fabrizio Loiacono, Paolo Canevali, Francesca Bellora, Claudia Tuberosa, Franco Locatelli, Concetta Micalizzi, Alessandro Moretta, Maria C Mingari, Lorenzo Moretta, Maurizio Aricò, Cristina Bottino, Daniela Pende
X-linked lymphoproliferative disease 1 (XLP1) is an inherited immunodeficiency, caused by mutations in SH2D1A encoding Signaling Lymphocyte Activation Molecule (SLAM)-associated protein (SAP). In XLP1, 2B4, upon engagement with CD48, has inhibitory instead of activating function. This causes a selective inability of cytotoxic effectors to kill EBV-infected cells, with dramatic clinical sequelae. Here, we investigated the NK cell education in XLP1, upon characterization of killer Ig-like receptor (KIR)/KIR-L genotype and phenotypic repertoire of self-HLA class I specific inhibitory NK receptors (self-iNKRs)...
April 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28386905/butyrophilin-3a-btn3a-cd277-specific-antibody-20-1-differentially-activates-v%C3%AE-9v%C3%AE-2-tcr-clonotypes-and-interferes-with-phosphoantigen-activation
#18
Lisa Starick, Felipe Riano, Mohindar M Karunakaran, Volker Kunzmann, Jianqiang Li, Matthias Kreiss, Sabine Amslinger, Emmanuel Scotet, Daniel Olive, Gennaro De Libero, Thomas Herrmann
Phosphoantigens (PAg) like HMBPP ((E)-4-hydroxy-3-methyl-but-2-enyl diphosphate) and butyrophilin 3 (BTN3A, CD277)-specific monoclonal antibody (mAb) 20.1 induce TCR-mediated activation of Vγ9Vδ2 T cells. Here, we compared murine reporter cells transduced with Vγ9Vδ2 TCRs G115, D1C55 and MOP for the activation in culture with human RAJI cells and PAgs or mAb 20.1 and its single chain derivative (sc). All transductants responded readily to PAg but only TCR MOP γ-chain-expressing cells responded to mAb/sc 20...
April 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28383204/monocytic-myeloid-derived-suppressor-cells-regulate-t-cell-responses-against-vaccinia-virus
#19
Carl Fortin, Yiping Yang, Xiaopei Huang
Vaccinia virus (VV) can potently activate NK- and T-cell responses, leading to efficient viral control and generation of long-lasting protective immunity. However, immune responses against viral infections are often tightly controlled to avoid collateral damage and systemic inflammation. We have previously shown that granulocytic myeloid-derived suppressor cells (g-MDSCs) can suppress the NK-cell response to VV infection. It remains unknown what regulates T-cell responses to VV infection in vivo. In this study, we first showed that monocytic MDSCs (m-MDSCs), but not g-MDSCs, from VV-infected mice could directly suppress CD4(+) and CD8(+) T-cell activation in vitro...
April 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28383107/a-mouse-model-of-systemic-lupus-erythematosus-responds-better-to-soluble-taci-than-to-soluble-baffr-correlating-with-depletion-of-plasma-cells
#20
Philipp Haselmayer, Michele Vigolo, Josquin Nys, Pascal Schneider, Henry Hess
The TNF family cytokines B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) support plasma cell survival. It is known that inhibitors of BAFF only (BAFFR-Fc) or BAFF and APRIL (TACI-Fc) administered early enough in an NZB/NZW F1 mouse model of systemic lupus erythematosus (SLE) ameliorate clinical outcomes, pointing to a pathogenic role of BAFF. In the present study, TACI-Fc administrated at a later stage of disease, after onset of autoimmunity, decreased the number of bone marrow plasma cells and slowed down further formation of autoantibodies...
April 6, 2017: European Journal of Immunology
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