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European Journal of Immunology

Simone Dudek, Sabrina Weißmüller, Martina Anzaghe, Lilija Miller, Sarah Sterr, Katja Hoffmann, Hartmut Hengel, Zoe Waibler
The first-in-human clinical trial of the CD28-specific monoclonal antibody (mAb) TGN1412 resulted in a life-threatening cytokine-release-syndrome. Although TGN1412 was designed as IgG4, known for weak Fc:Fcγ receptor (FcγR) interactions, these interactions contributed to TGN1412-induced T cell activation. Using cell lines (TFs) expressing human FcγRI, -IIa, -IIb or -III we show that TGN1412 and TGN1412 as IgG1 and IgG2 are bound by FcγRs as it can be deduced from literature. However, upon co-culture of TGN1412-decorated T cells with TFs or human primary blood cells, we observed that binding capacities by FcγRs do not correlate with the strength of the mediated effector function...
April 19, 2019: European Journal of Immunology
Mokarram Hossain, Paul Kubes
There is a close association between inflammation and sterile injury, however not all sterile injuries are the same. While a regulated inflammatory response is crucial for proper healing, a dysregulated or non-terminating response leads to disrepair. While immune cells are thought to contribute to the disrepair, they may also be critical for proper healing and as such their actions may dictate the end result. In all forms of sterile injury, release of damage-associated molecular patterns from necrotic cells causes robust recruitment of innate immune cells...
April 19, 2019: European Journal of Immunology
Sasha Silva-Barrios, Simona Stäger
Visceral leishmanisiais, a chornic, potentially fatal disease, is characterized by high production of low-affinity antibodies. In humans, hypergammaglobulinemia is prediction of disease progression. Nevertheless, the contribution of hypermutated and/or class-switched immunoglobulins to disease pathogenesis has never been studied. Using Aicda-/- mice and the experimental model of Leishmania donovani infection, we demonstrate that the absence of hypermutated and/or class-switched antibodies was associated with increased resistance to disease, stronger protective Th1 responses and a lower frequency of regulatory IFNγ+ IL-10+ CD4 T cells...
April 18, 2019: European Journal of Immunology
Ruud P H Raijmakers, Anne F M Jansen, Stephan P Keijmel, Jos W M van der Meer, Leo A B Joosten, Mihai G Netea, Chantal P Bleeker-Rovers
Besides fatigue, many Q fever fatigue syndrome (QFS) patients also complain of frequently recurring upper respiratory tract infections with severe symptoms. We investigated whether immunologic dysregulation contributes to these complaints. Cytokine and chemokine production was measured after stimulating monocytes of QFS patients and sex-matched healthy controls with LPS and several viral ligands. The H3K4me3 mark of open chromatin was measured at the promoter regions of cytokines and chemokines that differed significantly from healthy controls...
April 18, 2019: European Journal of Immunology
Elvira Stefania Cannizzo, Maddalena Cerrone, Esther Merlini, Bonnie van Wilgenburg, Leo Swadling, Giuseppe Ancona, Anna De Bona, Antonella d'Arminio Monforte, Paul Klenerman, Giulia Marchetti
XXXXXXXX This article is protected by copyright. All rights reserved.
April 15, 2019: European Journal of Immunology
Denise A Perez, Izabela Galvão, Rayssa M Athayde, Barbara M Rezende, Juliana P Vago, Julia D Silva, Alesandra C Reis, Lucas S Ribeiro, José H S Gomes, Rodrigo M Pádua, Fernão C Braga, Lirlândia P Sousa, Mauro M Teixeira, Vanessa Pinho
Sphingosine-1-phosphate (S1P) is an important sphingolipid derived from plasma membrane and has a known role in productive phase of inflammation, but its role in neutrophil survival and resolution phase of inflammation is unknown. Here, we investigated the effects of inhibition of S1P receptors and the blockade of S1P synthesis in BALB/c mice and human neutrophils. S1P and S1PR1-3 receptors expression were increased in cells from the pleural cavity stimulated with lipopolysaccharide (LPS). Using different antagonists of S1PRs and inhibitors of different steps of the metabolic pathway of S1P production, we show that S1P and its receptors are involved in regulating neutrophil survival and resolution of inflammation in the pleural cavity...
April 2, 2019: European Journal of Immunology
Marion Rolot, Annette Dougall, Justine Javaux, François Lallemand, Bénédicte Machiels, Philippe Martinive, Laurent Gillet, Benjamin G Dewals
Alternatively-activated Mφs (AAMφ) accumulate in hepatic granulomas during schistosomiasis and have been suggested to originate in the bone marrow. What is less understood is how these Mφ responses are regulated after S. mansoni infection. Here, we investigated the role of IL-4 receptor α-chain (IL-4Rα)-signalling in the dynamics of liver Mφ responses. We observed that IL-4Rα signalling was dispensable for the recruitment of Ly6Chi monocytes and for their conversion into F4/80hi CD64hi CD11bhi Mφ. Moreover, while IL-4Rα provided an AAMφ phenotype to liver F4/80hi CD64hi CD11bhi Mφ that was associated with regulation of granuloma formation, it was dispensable for host survival...
March 28, 2019: European Journal of Immunology
Angela Chiew Wen Ch'ng, Soo Khim Chan, Joshua Ignatius, Theam Soon Lim
The application of human T cell receptors (TCR) in cancer immunotherapy has gained momentum with developments in tumor killing strategies using endogenous adaptive immune responses. The successful coverage of a diverse TCR repertoire is mainly attributed to the primer design of the human TCR V genes. Here, we present a refined primer design strategy of the human TCR V gene by clustering V gene sequence homolog for degenerate primer design based on the data from IMGT. The primers designed were analyzed and the polymerase chain reaction (PCR) efficiency of each primer set was optimized...
March 28, 2019: European Journal of Immunology
Priscila Carneiro Campos, Marco Túlio Ribeiro Gomes, Fábio Antônio Vitarelli Marinho, Erika Sousa Guimarães, Mariza Gabriela Faleiro de Moura Lodi Cruz, Sergio Costa Oliveira
NLRP3 inflammasome is a protein complex crucial to caspase-1 activation and IL-1β and IL-18 maturation. This receptor participates in innate immune responses to different pathogens, including the bacteria of genus Brucella. Our group recently demonstrated that Brucella abortus-induced IL-1β secretion involves NLRP3 inflammasome and it is partially dependent on mitochondrial ROS production. However, other factors could be involved, such as P2X7-dependent potassium efflux, membrane destabilization, and cathepsin release...
March 28, 2019: European Journal of Immunology
Claudine Joseph, Jihene Klibi, Ludivine Amable, Lorenzo Comba, Alessandro Cascioferro, Marc Delord, Veronique Parietti, Christelle Lenoir, Sylvain Latour, Bruno Lucas, Christophe Viret, Antoine Toubert, Kamel Benlagha
It is established that iNKT cells are a cell type that require strong T cell receptor (TCR) signal for their proper development and represent a model for thymic agonist selection. The nature of the signal perceived by iNKT cells promoting their specification is not well understood. To address this question we analyzed iNKT cell development in relevant TCR Vα14-Jα18 alpha chain transgenic mice (Vα14Tg). In CD4-Vα14Tg mice, where the transgene is driven by CD4 promoter, we identified a block in iNKT cell development at early developmental stages due to a reduced expression of key transcription factors accompanied with a reduced TCR expression levels...
March 26, 2019: European Journal of Immunology
Steven de Jesus Carrion, Serena Abbondante, Heather L Clark, Michaela E Marshall, Isabelle Mouyna, Anne Beauvais, Yan Sun, Patricia R Taylor, Sixto M Leal, Brittany Armstrong, William Carrera, Jean-Paul Latge, Eric Pearlman
Aspergillus fumigatus is an important cause of pulmonary and systemic infections in immune compromised individuals, and of corneal ulcers and blindness in immune competent patients. To examine the role of chitin synthases in Aspergillus corneal infection, we analyzed Aspergillus mutants of chitin synthase family 1 and family 2, and found that the quadruple mutants from both families were more readily killed by neutrophils in vitro, and that both exhibited an impaired ability to grow in the cornea. Further, inhibition of chitin synthases using Nikkomycin Z enhanced neutrophil killing in vitro and in vivo in a murine model of A...
March 23, 2019: European Journal of Immunology
Ling Xiao, Wouter Rph van De Worp, Roderick Stassen, Celine Van Maastrigt, Nienke Kettelarij, Bernd Stahl, Bernadet Blijenberg, Saskia A Overbeek, Gert Folkerts, Johan Garssen, Belinda Van't Land
Human milk oligosaccharides (HMOS) are a complex mixture of bioactive components supporting the immune development of breastfed-infants. Dendritic cells (DCs) play a central role in the regulation of immune responses, being specialized in antigen presentation and driving T-cell priming as well as differentiation. However, little is known about the direct effects of HMOS on human DC phenotypes and functions. Here, we report that HMOS mixture isolated from pooled human milk, induced semi-maturation of human monocytes-derived DCs (moDCs), and elevated levels of IL-10, IL-27 and IL-6 but not IL-12p70 and TNF-α...
March 22, 2019: European Journal of Immunology
Raquel de la Varga-Martínez, Beatriz Rodríguez-Bayona, Antonio Campos-Caro, Gustavo A Añez, Fermín Medina-Varo, Carmen Rodríguez
Systemic lupus erythematosus and rheumatoid arthritis are autoimmune diseases characterised by B-cell hyperactivation and production of autoantibodies (AutoAbs) against various self-antigens, including extractable nuclear antigens and citrullinated peptides. Therefore, B lymphocytes and antibody-secreting cells are considered relevant targets for therapies. However, isolation and characterisation of auto-reactive specific B lymphocytes are limited, primarily due to technical issues. In this work, we purified extractable nuclear antigen-specific and citrullinated peptide-specific auto-reactive B lymphocytes by magnetic selection with ENA- and citrullinated peptide-bound immunobeads...
March 20, 2019: European Journal of Immunology
Paul Rj Ames, Mira Merashli, Fabrizio Gentile
No abstract text is available yet for this article.
March 20, 2019: European Journal of Immunology
Thomas Hochdörfer, Carla Winkler, Katerina Pardali, Jenny Mjösberg
Human type 2 innate lymphoid cells (ILC2) are the only ILC subset that shows heterogeneous expression of the stem cell factor (SCF) receptor c-Kit (CD117). Despite its use as surface marker to distinguish ILC populations, its influence on ILC2 biology has not been investigated. Here we show that c-Kit expression of peripheral blood ILC distinguishes two functionally distinct ILC2 subsets (c-Kithi and c-Kitlo ). When examined for their potential for functional plasticity we found that c-Kitlo ILC2 displayed greater potential to produce type 2 cytokines, possibly representing fully mature and lineage committed ILC2...
March 20, 2019: European Journal of Immunology
Bojan Stojanovic, Ivan Jovanovic, Bojana S Stojanovic, Milica Dimitrijevic Stojanovic, Nevena Gajovic, Gordana Radosavljevic, Jelena Pantic, Nebojsa Arsenijevic, Miodrag L Lukic
Acute pancreatitis is characterized by autodigestion of pancreatic cells followed by acute inflammation leading to pathology and death. In experimental acute pancreatitis, pancreatic acinar cells and infiltrating macrophages express Galectin-3 but its role in pathology of this disease is unknown. Therefore, we studied its role using Galectin-3 deficient mice. Deletion of Galectin-3 prolonged the survival of mice, led to attenuation of histopathology, decreased infiltration of mononuclear cells and neutrophils that express TLR-4, in particular, pro-inflammatory N1 neutrophils...
March 20, 2019: European Journal of Immunology
Maria F Pascutti, Sulima Geerman, Nicholas Collins, Giso Brasser, Benjamin Nota, Regina Stark, Felix Behr, Anna Oja, Edith Slot, Eleni Panagioti, Julia E Prier, Sarah Hickson, Monika C Wolkers, Mirjam H M Heemskerk, Pleun Hombrink, Ramon Arens, Laura K Mackay, Klaas P J M van Gisbergen, Martijn A Nolte
Bone marrow (BM) has been put forward as a major reservoir for memory CD8+  T cells. In order to fulfill that function, BM should "store" memory CD8+ T cells, which in biological terms would require these "stored" memory cells to be in disequilibrium with the circulatory pool. This issue is a matter of ongoing debate. Here, we unequivocally demonstrate that murine and human BM harbors a population of tissue-resident memory CD8+ T (TRM ) cells. These cells develop against various pathogens, independently of BM infection or local antigen recognition...
March 20, 2019: European Journal of Immunology
Guillemette Masse-Ranson, Mathilde Dusséaux, Oriane Fiquet, Sylvie Darche, Maud Boussand, Yan Li, Silvia Lopez-Lastra, Nicolas Legrand, Erwan Corcuff, Antoine Toubert, Mireille Centlivre, Timothée Bruel, Hergen Spits, Olivier Schwartz, Yves Lévy, Hélène Strick-Marchand, James P Di Santo
Human Immune System (HIS) mouse models provide a robust in vivo platform to study human immunity. Nevertheless, the signals that guide human lymphocyte differentiation in HIS mice remain poorly understood. Here, we have developed a novel Balb/c Rag2-/- Il2rg-/- SirpaNOD (BRGS) HIS mouse model expressing human HLA-A2 and -DR2 transgenes (BRGSA2DR2). When comparing BRGS and BRGSA2DR2 HIS mice engrafted with human CD34+ stem cells, a more rapid emergence of T cells in the circulation of hosts bearing human HLA was shown, which may reflect a more efficient human T cell development in the mouse thymus...
March 19, 2019: European Journal of Immunology
Rongjian Hong, Nannan Lai, Rika Ouchida, Ermeng Xiong, Yang Zhou, Qing Min, Jun Liu, Yue Tang, Masaki Hikida, Takeshi Tsubata, Yanqing Wang, Ji-Yang Wang
The B cell receptor (BCR) plays a central role in B cell development, survival, activation and differentiation. We have identified the B cell novel protein 1 (BCNP1) as a new regulator of BCR signaling. BCNP1 contains a pleckstrin homology domain, 3 proline-rich motifs and a potential SH2 binding site, and is predominantly expressed by B cells. We found that BCNP1 overexpression in WEHI231 immature B cells potentiated α-IgM-induced apoptosis. Conversely, BCNP1-deficient WEHI231 cells, generated by CRISPR-Cas9-mediated genome editing, exhibited reduced apoptosis after BCR crosslinking...
March 19, 2019: European Journal of Immunology
Monique Garcia, Alana Santos-Dias, André Luis Lacerda Bachi, Manoel Carneiro Oliveira-Junior, Adilson Santos Andrade-Souza, Sérgio César Ferreira, Jefferson Comin Jonco Aquino-Junior, Francine Maria Almeida, Nicole Cristine Rigonato-Oliveira, Ana Paula Ligeiro Oliveira, Luiz Eduardo Baggio Savio, Robson Coutinho-Silva, Tobias Müller, Marco Idzko, Timo Siepmann, Rodolfo Paula Vieira
Creatine is a substrate for adenosine triphosphate synthesis, and it is the most used dietary supplement among professional and recreative athletes and sportsmen. Creatine supplementation may increase allergic airway response, but the cellular and molecular mechanisms are unknown. We used murine model of ovalbumin (OVA)-induced chronic asthma asthma and showed that creatine (Cr) supplementation increased total proteins, ATP level, lymphocytes, macrophages and IL-5 levels in bronchoalveolar lavage fluid, as well as IL-5 in the supernatant of re-stimulated mediastinal lymph nodes...
March 19, 2019: European Journal of Immunology
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