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European Journal of Immunology

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https://www.readbyqxmd.com/read/28643847/ncr1-deficiency-diminishes-the-generation-of-protective-murine-cytomegalovirus-antibodies-by-limiting-follicular-helper-t-cell-maturation
#1
Antonija Miletic, Maja Lenartic, Branka Popovic, Ilija Brizic, Tihana Trsan, Karmela Miklic, Ofer Mandelboim, Astrid Krmpotic, Stipan Jonjic
NKp46/NCR1 is an activating NK-cell receptor implicated in the control of various viral and bacterial infections. Recent findings also suggest that it plays a role in shaping the adaptive immune response to pathogens. Using NCR1-deficient (NCR1(gfp/gfp) ) mice we provide evidence for the role of NCR1 in antibody response to mouse cytomegalovirus infection (MCMV). The absence of NCR1 resulted in impaired maturation, function and NK-cell migration to regional lymph nodes. In addition, CD4(+) T-cell activation and follicular helper T-cell (Tfh) generation were reduced, leading to inferior germinal center (GC) B-cell maturation...
June 23, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28631311/the-il-10-stat3-axis-contributions-to-immune-tolerance-by-thymus-and-peripherally-derived-regulatory-t-cells
#2
REVIEW
Klaus G Schmetterer, Winfried F Pickl
The signal transducer and activator of transcription (STAT) proteins are important mediators for the integration of extrinsic signals provided by cytokines and hormones and thereby adapt cellular processes to their surroundings. In the past decade, the involvement of STAT3 in the regulation of T-cell responses has become a topic of increasing interest. STAT3 is activated in response to multiple cytokines, many of which have been shown to influence T-cell responses. Interestingly, many of these factors have been described with apparent opposing roles, such as the highly pro-inflammatory potency of IL-6 and the anti-inflammatory properties of IL-10, thus raising the possibility that STAT3 signaling may fulfill diverse roles in CD4(+) T-cells...
June 20, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28631301/prevention-of-lupus-nephritis-development-in-nzb-nzw-mice-by-selective-blockade-of-cd28
#3
Laetitia Laurent, Awena Lefur, Rozenn Le Bloas, Mélanie Néel, Caroline Mary, Anne Moreau, Nicolas Poirier, Bernard Vanhove, Fadi Fakhouri
Systemic Lupus Erythematosus (SLE) is a chronic systemic inflammatory disease. Autoantibodies (autoAbs) against double-stranded DNA (ds DNA), the hallmark of lupus, are produced and maintained by the interaction between auto-reactive B cells and CD4(+) T cells. This interplay is controlled by the CD28/CD80-86/CTLA-4 axis. Here we investigated whether selective blockade of CD28-CD80/86 co-stimulatory interactions abrogates lupus nephritis development in a murine model of SLE. To this aim, NZB/NZW F1 mice were treated for 3 months, either with an anti-CD28 Fab' fragment or a control Fab'-IgG...
June 20, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28613415/composition-and-functionality-of-the-intrahepatic-innate-lymphoid-cell-compartment-in-human-non-fibrotic-and-fibrotic-livers
#4
Marianne Forkel, Lena Berglin, Eliisa Kekäläinen, Adrian Carlsson, Emma Svedin, Jakob Michaëlsson, Maho Nagasawa, Jonas S Erjefält, Michiko Mori, Malin Flodström-Tullberg, Annika Bergquist, Hans-Gustaf Ljunggren, Magnus Westgren, Ulrik Lindforss, Danielle Friberg, Carl Jorns, Ewa Ellis, Niklas K Björkström, Jenny Mjösberg
Human innate lymphoid cells have been described to exist in different organs, with functional deregulation of these cells contributing to several disease states. Here, we performed the first detailed characterization of the phenotype, tissue-residency properties and functionality of ILC1s, ILC2s and ILC3s in the human adult and fetal liver. In addition, we investigated changes in the ILC compartment in liver fibrosis. A unique composition of tissue-resident ILCs was observed in non-fibrotic livers as compared with that in mucosal tissues, with NKp44(-) ILC3s accounting for the majority of total intrahepatic ILCs...
June 14, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28612942/cytomegalovirus-vector-expressing-rae-1%C3%AE-induces-enhanced-anti-tumor-capacity-of-murine-cd8-t-cells
#5
Tihana Tršan, Kristina Vuković, Petra Filipović, Ana Lesac Brizić, Niels A W Lemmermann, Kilian Schober, Dirk H Busch, William J Britt, Martin Messerle, Astrid Krmpotić, Stipan Jonjić
Designing CD8(+) T-cell vaccines, which would provide protection against tumors is still considered a great challenge in immunotherapy. Here we show the robust potential of cytomegalovirus (CMV) vector expressing the NKG2D ligand RAE-1γ as CD8(+) T cell-based vaccine against malignant tumors. Immunization with the CMV vector expressing RAE-1γ, delayed tumor growth or even provided complete protection against tumor challenge in both prophylactic and therapeutic settings. Moreover, a potent tumor control in mice vaccinated with this vector can be further enhanced by blocking the immune checkpoints TIGIT and PD-1...
June 14, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28612433/musculin-inhibits-human-t-helper-17-cell-response-to-interleukin-2-by-controlling-stat5b-activity
#6
Veronica Santarlasci, Alessio Mazzoni, Manuela Capone, Maria Caterina Rossi, Laura Maggi, Gianni Montaini, Beatrice Rossettini, Rolando Cimaz, Matteo Ramazzotti, Giusi Barra, Raffaele De Palma, Enrico Maggi, Francesco Liotta, Lorenzo Cosmi, Sergio Romagnani, Francesco Annunziato
We recently demonstrated that human T helper (Th) 17 cells, unlike Th1 cells, do not proliferate in response to T-cell receptor stimulation, mainly because of their reduced capacity to produce and respond to IL-2. In this study we show that their lower responsiveness to IL-2 is due to the selective expression of Musculin (MSC), a member of the basic helix-loop-helix transcription factors. We show that MSC expression in human Th17 cells is retinoic acid orphan receptor (ROR)γt-dependent, and allows the up-regulation of PPP2R2B, a regulatory member of the protein phosphatase 2A (PP2A) enzyme...
June 14, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28608550/a-new-staining-protocol-for-detection-of-murine-antibody-secreting-plasma-cell-subsets-by-flow-cytometry
#7
Katharina Pracht, Julia Meinzinger, Patrick Daum, Sebastian R Schulz, Dorothea Reimer, Manuela Hauke, Edith Roth, Dirk Mielenz, Claudia Berek, Joana Côrte-Real, Hans-Martin Jäck, Wolfgang Schuh
In mice, CD138, B220 and Blimp1, a plasma cell (PC) signature transcription factor, are frequently used to quantify mature antibody-secreting PCs. Here, we show in a Blimp1:GFP reporter mouse that the CD138(hi) /B220(low) population in bone marrow (BM) contains a significant fraction of Blimp1-negative cells. Therefore, detection of B220 and CD138 alone is not sufficient to identify PCs unambiguously. To circumvent this problem, we developed a new 4-color PC staining protocol using antibodies against CD138, B220, transmembrane activator and CAML interactor (TACI) and CD19...
June 13, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28608405/revisiting-the-specificity-of-the-mhc-class%C3%A2-ii-transactivator-ciita-in-classical-murine-dendritic-cells-in-vivo
#8
David A Anderson, Gary E Grajales-Reyes, Ansuman T Satpathy, Carlos E Vasquez Hueichucura, Theresa L Murphy, Kenneth M Murphy
Ciita was discovered for its role in regulating transcription of major histocompatibility complex class II (MHCII) genes. Subsequently, CIITA was predicted to control many other genes based on reporter and ChIP-seq analysis but few such predictions have been verified in vivo using Ciita(-/-) mice. Testing these predictions for classical dendritic cells (cDCs) has been particularly difficult, since Ciita(-/-) mice lack MHCII expression required to identify cDCs. However, recent identification of the cDC-specific transcription factor Zbtb46 allows identification of cDCs independently of MHCII expression...
June 13, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28605013/the-strength-of-bcr-signaling-shapes-terminal-development-of-follicular-helper-t-cells-in-mice
#9
Antoine Sacquin, Mylène Gador, Nicolas Fazilleau
Antibody production is key for effective immune response and relies on follicular helper T (Tfh) cells. B cell-Tfh cell interactions result either in an extra-follicular low affinity B-cell response or in germinal center reactions producing high-affinity memory B cells and long-lived plasma cells. As Tfh cells influence B-cell commitment, it also became clear that B cells influence these interactions in ways that still remain unresolved. We observed that strong BCR signals decreased Tfh-cell differentiation in vitro, which correlated with decreased expression of ICOS-L at the surface of stimulated B cells...
June 12, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28598502/balanced-bcl-3-expression-in-murine-cd4-t-cells-is-required-for-generation-of-encephalitogenic-th17-cells
#10
Ilgiz A Mufazalov, Janina Kuschmann, David Andruszewski, Joumana Masri, Laureen A Gabriel, Petra Adams, Sonja Reissig, Nadine Hövelmeyer, Ari Waisman
The function of NF-κB family members is controlled by multiple mechanisms including the transcriptional regulator Bcl-3, an atypical member of the IκB family. By using a murine model of conditional Bcl-3 overexpression specifically in T cells, we observed impairment in the development of Th2, Th1 and Th17 cells. High expression of Bcl-3 promoted CD4(+) T-cell survival, but at the same time suppressed proliferation in response to TCR stimulation, resulting in reduced CD4(+) T-cell expansion. As a consequence, T cell specific overexpression of Bcl-3 led to reduced inflammation in the small intestine of mice applied with anti-CD3 in a model of gut inflammation...
June 9, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28586167/card9-dependent-il-1%C3%AE-regulates-il-22-production-from-group-3-innate-lymphoid-cells-and-promotes-colitis-associated-cancer
#11
Hanna Bergmann, Susanne Roth, Konstanze Pechloff, Elina A Kiss, Sabine Kuhn, Mathias Heikenwälder, Andreas Diefenbach, Florian R Greten, Jürgen Ruland
Inflammatory bowel diseases (IBD) are key risk factors for the development of colorectal cancer, but the mechanisms that link intestinal inflammation with carcinogenesis are insufficiently understood. Card9 is a myeloid cell-specific signaling protein that regulates inflammatory responses downstream of various pattern recognition receptors and which cooperates with the inflammasomes for IL-1β production. Because polymorphisms in Card9 were recurrently associated with human IBD, we investigated the function of Card9 in a colitis-associated cancer (CAC) model...
June 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28586109/fyn-kinase-mediates-cortical-actin-ring-depolymerization-required-for-mast-cell-migration-in-response-to-tgf-%C3%AE-in-mice
#12
Karla A Ramírez-Valadez, Genaro Vázquez-Victorio, Marina Macías-Silva, Claudia González-Espinosa
Transforming Growth Factor-β (TGF-β) is a potent mast cell (MC) chemoattractant able to modulate local inflammatory reactions. The molecular mechanism leading to TGF-β-directed MC migration is not fully described. Here we analyzed the role of the Src family protein kinase Fyn on the main TGF-β-induced cytoskeletal changes leading to MC migration. Utilizing bone marrow-derived mast cells (BMMCs) from WT and Fyn-deficient mice we found that BMMC migration to TGF-β was impaired in the absence of the kinase...
June 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28586108/bcl6-promotes-follicular-helper-t-cell-differentiation-and-pd-1-expression-in-a-blimp1-independent-manner-in-mice
#13
Markus M Xie, Byung-Hee Koh, Kristin Hollister, Hao Wu, Jie Sun, Mark H Kaplan, Alexander L Dent
The transcription factors Bcl6 and Blimp1 have opposing roles in the development of the follicular helper T (TFH ) cells: Bcl6 promotes and Blimp1 inhibits TFH -cell differentiation. Similarly, Bcl6 activates, while Blimp1 represses, expression of the TFH -cell marker PD-1. However, Bcl6 and Blimp1 repress each other's expression, complicating the interpretation of the regulatory network. Here we sought to clarify the extent to which Bcl6 and Blimp1 independently control TFH -cell differentiation by generating mice with T-cell specific deletion of both Bcl6 and Blimp1 (double conditional KO [dcKO] mice)...
June 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28586095/cmv-drives-the-expansion-of-highly-functional-memory-t-cells-expressing-nk-cell-receptors-in-renal-transplant-recipients
#14
Nandina Makwana, Bree Foley, Sonia Fernandez, Silvia Lee, Ashley Irish, Hanspeter Pircher, Patricia Price
Cytomegalovirus (CMV) is a common opportunistic infection encountered in renal transplant recipients (RTRs) and may be reactivated without symptoms at any time post-transplant. We describe how active and latent CMV affect T-cell subsets in RTRs who are stable on maintenance therapy. T-cell responses to CMV were assessed in RTRs (n = 54) >2 years post-transplant, and healthy controls (n = 38). Seven RTRs had CMV DNA detectable in plasma. CMV antibody and DNA aligned with increased proportions of CD8+ T cells and reduced CD4/CD8 ratios...
June 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28555838/spontaneous-cd4-and-cd8-t-cell-responses-directed-against-cancer-testis-antigens-are-present-in-the-peripheral-blood-of-testicular-cancer-patients
#15
Hayden Pearce, Paul Hutton, Shalini Chaudhri, Emilio Porfiri, Prashant Patel, Richard Viney, Paul Ah Moss
Cancer/Testis Antigen (CTAg) expression is restricted to spermatogenic cells in an immune-privileged site within the testis. However, these proteins are expressed aberrantly by malignant cells and T cell responses against CTAgs develop in many cancer patients. We investigated the prevalence, magnitude and phenotype of CTAg-specific T cells in the blood of patients with testicular germ cell tumors (TGCTs). CD8(+) and CD4(+) T cell responses against MAGE-A family antigens were present in 44% (20/45) of patients' samples assayed by ex vivo IFN-γ ELISPOT...
May 28, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28555727/targeting-jak-stat-signalling-in-inflammatory-skin-diseases-with-small-molecule-inhibitors
#16
Katharina Welsch, Julia Holstein, Arian Laurence, Kamran Ghoreschi
For most inflammatory skin diseases topical glucocorticosteroids and traditional oral immunosuppressive drugs remain the principle treatment choices, but this has started to change. A deeper understanding in individual disease pathogenesis, basic immune mechanisms and molecular signalling pathways, together with advances in pharmaceutical drug development, allow us to interfere more precisely with disease-related factors. Some examples of inflammation-controlling interventions include antibodies neutralizing disease-associated cytokines, and small molecules targeting intracellular pathways relevant to cytokine production or cytokine signalling...
May 28, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28543188/cd44-deletion-leading-to-attenuation-of-experimental-autoimmune-encephalomyelitis-results-from-alterations-in-gut-microbiome-in-mice
#17
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 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 CD44 knockout (CD44KO) mice. Fecal transfer from naïve CD44KO but not C57BL/6 wild type (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
#18
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
#19
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
#20
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
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