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European Journal of Immunology

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https://www.readbyqxmd.com/read/29150834/il-22-neutralizing-autoantibodies-impair-fungal-clearance-in-murine-oropharyngeal-candidiasis-model
#1
Rudolf Bichele, Jaanika Kärner, Kai Truusalu, Imbi Smidt, Reet Mändar, Heather R Conti, Sarah L Gaffen, Pärt Peterson, Martti Laan, Kai Kisand
Protection against mucocutaneous candidiasis depends on the T helper (Th)17 pathway, as gene defects affecting its integrity result in inability to clear Candida albicans infection on body surfaces. Moreover, autoantibodies neutralizing Th17 cytokines have been related to chronic candidiasis in a rare inherited disorder called autoimmune polyendocriopathy candidiasis ectodermal dystrophy (APECED) caused by mutations in autoimmune regulator (AIRE) gene. However, the direct pathogenicity of these autoantibodies has not yet been addressed...
November 17, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29150831/the-extracellular-membrane-proximal-domain-of-membrane-bound-ige-restricts-b-cell-activation-by-limiting-b-cell-antigen-receptor-surface-expression
#2
Kanika Vanshylla, Felipe Opazo, Konrad Gronke, Jürgen Wienands, Niklas Engels
Immunoglobulin E (IgE) antibodies are key mediators of allergic reactions. Due to their potentially harmful anaphylactic properties their production is tightly regulated. The membrane-bound isoform of IgE (mIgE), which is an integral component of the B cell antigen receptor, has been shown to be critical for the regulation of IgE responses in mice. In primate species including humans, mIgE can be expressed in two isoforms that are produced by alternative splicing of the primary ε Ig heavy chain transcript, and differ in the absence or presence of an extracellular membrane-proximal domain (EMPD) consisting of 52 amino acids...
November 17, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29148561/the-role-of-il-23-receptor-signaling-in-inflammation-mediated-erosive-autoimmune-arthritis-and-bone-remodeling
#3
REVIEW
Wida Razawy, Marjolein van Driel, Erik Lubberts
The IL-23/Th17 axis has been implicated in the development of autoimmune diseases, such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA). RA and PsA are heterogeneous diseases with substantial burden on patients. Increasing evidence suggests that the IL-23 signaling pathway may be involved in the development of autoimmunity and erosive joint damage. IL-23 can act either directly or indirectly on bone forming osteoblasts as well as on bone resorbing osteoclasts. As IL-23 regulates the activity of cells of the bone, it is conceivable that in addition to inflammation-mediated joint erosion, IL-23 may play a role in physiological bone remodeling...
November 17, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29148036/function-and-mechanism-of-the-pyrin-inflammasome
#4
REVIEW
Rosalie Heilig, Petr Broz
Pyrin, encoded by the MEFV gene, is an intracellular pattern recognition receptor that assembles inflammasome complexes in response to pathogen infections. Mutations in the MEFV gene have been linked to autoinflammatory diseases such as Familial Mediterranean Fever (FMF) or pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND). Recent insights have now revealed how pyrin is activated during infection, providing a molecular basis for the understanding of such disease-causing mutations in pyrin...
November 16, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29143318/calcineurin-inhibitor-induced-complement-system-activation-via-erk1-2-signalling-is-inhibited-by-socs-3-in-human-renal-tubule-cells
#5
Beatrix Loeschenberger, Lea Niess, Reinhard Würzner, Hubert Schwelberger, Iris E Eder, Martin Puhr, Julia Guenther, Jakob Troppmair, Michael Rudnicki, Hannes Neuwirt
One factor that significantly contributes to renal allograft loss is chronic calcineurin inhibitor (CNI) nephrotoxicity (CIN). Among other factors, the complement (C-) system has been proposed to be involved CIN development. Hence, we investigated the impact of CNIs on intracellular signalling and the effects on the C-system in human renal tubule cells. In a qPCR array, CNI treatment upregulated C-factors and downregulated SOCS-3 and the complement inhibitors CD46 and CD55. Additionally, ERK1/-2 was required for these regulations...
November 15, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29124751/detailed-characterization-of-human-mycobacterium-tuberculosis-specific-hla-e-restricted-cd8-t-cells
#6
Teresa Prezzemolo, Krista E van Meijgaarden, Kees Lmc Franken, Nadia Caccamo, Francesco Dieli, Tom Hm Ottenhoff, Simone A Joosten
HLA-E presented antigens are interesting targets for vaccination given HLA-Es' essentially monomorphic nature. We have shown previously that Mycobacterium tuberculosis (Mtb) peptides are presented by HLA-E to CD8(+) effector T-cells, but the precise phenotype and functional capacity of these cells remains poorly characterized. We have developed and utilized in this study a new protocol combining HLA-E tetramer with intracellular staining for cytokines, transcription factors and cytotoxic molecules to characterize these cells in depth...
November 9, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29120053/tumor-conditions-induce-bone-marrow-expansion-of-granulocytic-but-not-monocytic-immunosuppressive-leukocytes-with-increased-cxcr2-expression-in-mice
#7
Zhen Bian, Lei Shi, Mahathi Venkataramani, Ahmed Mansour Abdelaal, Courtney Culpepper, Koby Kidder, Hongwei Liang, Ke Zen, Yuan Liu
Myeloid-derived suppressor cells (MDSCs) promote tumor growth through, in part, inhibiting T cell immunity. However, mechanisms underlying MDSC expansion and guidance of MDSCs toward the tumor microenvironment remain unclear. Employing Percoll density gradients, we separate bone marrow (BM) leukocytes from tumor-bearing mice into four density-increasing bands with myeloid leukocytes enriched in bands III and IV. Band III comprises monocytes and low-density granulocytes, both confirmed to be M-MDSCs and G-MDSCs, respectively, by displaying potent inhibition of T cell proliferation...
November 9, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29108094/dimethyl-fumarate-treatment-alters-nk-cell-function-in-multiple-sclerosis
#8
LETTER
Matthew D Smith, Peter A Calabresi, Pavan Bhargava
No abstract text is available yet for this article.
November 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29105756/kir-downregulation-by-il-12-15-18-unleashes-human-nk-cells-from-kir-hla-i-inhibition-and-enhances-killing-of-tumor-cells
#9
Eva-Maria Ewen, Jens H W Pahl, Matthias Miller, Carsten Watzl, Adelheid Cerwenka
To exploit autologous NK cells for cancer immunotherapy, it is highly relevant to circumvent killer cell immunoglobulin-like receptor (KIR)-mediated self-inhibition of human NK cells by HLA-I-expressing tumor cells. Here, we show that stimulation of NK cells with IL-12/15/18 for two days leads to downregulation of surface expression of the inhibitory KIR2DL2/L3, KIR2DL1 and KIR3DL1 receptors on peripheral blood NK cells. Downregulation of KIR expression was attributed to decreased KIR mRNA levels which could be re-induced already 3 days after re-culture in IL-2...
November 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29080214/transcription-factor-yy1-can-control-aid-mediated-mutagenesis-in-mice
#10
Kristina Zaprazna, Arindam Basu, Nikola Tom, Vibha Jha, Suchita Hodawadekar, Lenka Radova, Jitka Malcikova, Boris Tichy, Sarka Pospisilova, Michael L Atchison
Activation-induced cytidine deminase (AID) is crucial for controlling the immunoglobulin (Ig) diversification processes of somatic hypermutation (SHM) and class switch recombination (CSR). AID initiates these processes by deamination of cytosine, ultimately resulting in mutations or double strand DNA breaks needed for SHM and CSR. Levels of AID control mutation rates, and off-target non-Ig gene mutations can contribute to lymphomagenesis. Therefore, factors that control AID levels in the nucleus can regulate SHM and CSR, and may contribute to disease...
October 28, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29067678/the-immunoproteasome-subunit-lmp7-is-required-in-the-murine-thymus-for-filling-up-a-hole-in-the-t-cell-repertoire
#11
Michael Basler, Sarah Mundt, Marcus Groettrup
Cells of hematopoietic origin express high levels of the immunoproteasome, a cytokine-inducible variant of the proteasome which has been implicated in regulating inflammatory responses and antigen presentation. In the thymus, medullary thymic epithelial cells (mTECs) and cortical thymic epithelial cells (cTECs) do express different proteasome subunits exerting chymotrypsin-like activities suggesting distinct functions in thymic T cell selection. Employing the lymphocytic choriomeningitis virus (LCMV) infection model, we could show that the immunoproteasome subunit LMP7 was absolutely required for the generation of LCMV GP118-125 -specific T cells although the class I mediated presentation of GP118-125 was not dependent on LMP7...
October 24, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29067676/myc-binding-protein-2-suppresses-m2-like-phenotypes-in-macrophages-during-zymosan-induced-inflammation-in-mice
#12
Sandra Pierre, Dong Dong Zhang, Jing Suo, Katharina Kern, Neda Tarighi, Klaus Scholich
MYCBP2 is an E3 ubiquitin ligase, which is well characterized as a key element in the inhibition of neuronal growth, synapse formation and synaptic strength by regulating several signaling pathways. Although MYCBP2 was suspected to be expressed also in immune cells, to date nothing is known about its role in inflammation. We used Multi-epitope ligand cartography (MELC), a method for multiple sequential immunohistology, to show that MYCBP2 is strongly expressed in monocyte-derived macrophages during zymosan-induced inflammation...
October 24, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29023682/short-term-cytokine-stimulation-reveals-regulatory-t%C3%A2-cells-with-down-regulated-foxp3-expression-in-human-peripheral-blood
#13
Paula Tabares, Susanne Berr, Daniela Langenhorst, Birgit Sawitzki, Ineke Ten Berge, Hans-Peter Tony, Thomas Hünig
The identification of regulatory T cells (Treg cells) in human peripheral blood is an important tool in diagnosis, research, and therapeutic intervention. As compared to lymphoid tissues, the frequencies of circulating Treg cells identified as CD4(+) CD25(+) Foxp3(+) are, however, low. We here show that many of these cells remain undetected due to transient down regulation of Foxp3, which rapidly decays in the absence of cytokine-mediated STAT5 signals. Short-term incubation of PBMCs or isolated CD4(+) T cells, but not of lymph node cells, with IL-2, -7, or -15 more than doubles the frequency of Foxp3(+) CD25(+) among CD4(+) T cells detectable by flow cytometry...
October 11, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28980305/ly6c-high-monocytes-facilitate-transport-of-murid-herpesvirus-68-into-inflamed-joints-of-arthritic-mice
#14
Manon LeBel, Benoit Egarnes, Alexandre Brunet, Patricia Lacerte, Alexandre Paré, Steve Lacroix, Jacques P Brown, Jean Gosselin
Viruses, particularly the Epstein-Barr virus (EBV) has long been suspected to exacerbate acute arthritic symptoms. However, the cell populations that contribute to import viruses into the inflamed tissues remain to be identified. In the present study, we have investigated the role of monocytes in the transport of Murid herpesvirus 68 (MHV-68), a mouse virus closely related to EBV, using the serum transfer-induced arthritis (STIA) model. We found compelling evidence that MHV-68 infection markedly increased disease severity in NR4A1-/- mice, which are deficient for Ly6C(low) monocytes...
October 5, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28980301/ly9-slamf3-receptor-differentially-regulates-inkt-cell-development-and-activation-in-mice
#15
Marta Cuenca, Joan Puñet-Ortiz, Maria Ruart, Cox Terhorst, Pablo Engel
Invariant natural killer T (iNKT) cells develop into three subsets (NKT1, NKT2, and NKT17) expressing a distinct transcription factor profile, which regulates cytokine secretion upon activation. iNKT cell development in the thymus is modulated by signaling lymphocytic activation molecule family (SLAMF) receptors. In contrast to other SLAMF members, Ly9 (SLAMF3) is a non-redundant negative regulator of iNKT cell development. Here, we show that Ly9 influences iNKT cell lineage differentiation. Ly9-deficient mice on a BALB/c background contained a significantly expanded population of thymic NKT2 cells, while NKT1 cells were nearly absent in BALB/c...
October 5, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28975614/t-cell-receptor-alpha-variable-12-2-bias-in-the-immunodominant-response-to-yellow-fever-virus
#16
Amandine Bovay, Vincent Zoete, Garry Dolton, Anna M Bulek, David K Cole, Pierre J Rizkallah, Anna Fuller, Konrad Beck, Olivier Michielin, Daniel E Speiser, Andrew K Sewell, Silvia A Fuertes Marraco
The repertoire of human αβ T cell receptors (TCRs) is generated via somatic recombination of germline gene segments. Despite this enormous variation, certain epitopes can be immunodominant, associated with high frequencies of antigen-specific T cells and/or exhibit bias towards a TCR gene segment. Here, we studied the TCR repertoire of the HLA-A*0201-restricted epitope LLWNGPMAV (hereafter, A2/LLW) from Yellow Fever virus, which generates an immunodominant CD8(+) T cell response to the highly effective YF-17D vaccine...
October 3, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28971472/asc-and-nlrp3-impair-host-defense-during-lethal-pneumonia-caused-by-serotype-3-streptococcus-pneumoniae-in-mice
#17
Miriam H P van Lieshout, Alex F de Vos, Mark C Dessing, Alexander P N A de Porto, Onno J de Boer, Regina de Beer, Sanne Terpstra, Sandrine Florquin, Cornelis Van't Veer, Tom van der Poll
Streptococcus (S.) pneumoniae is the most common cause of community-acquired pneumonia. The Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, consisting of NLRP3, ASC (the adaptor apoptosis-associated speck-like protein containing a CARD) and caspase-1, has been implicated in protective immunity during pneumonia induced by high doses of S. pneumoniae serotype 2. Here we investigated the role of the NLRP3 inflammasome in the host response during lethal airway infection with a low dose of serotype 3 S...
October 2, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28960320/cmv-and-natural-killer-cells-shaping-the-response-to-vaccination
#18
REVIEW
Martin R Goodier, Stipan Jonjić, Eleanor M Riley, Vanda Juranić Lisnić
Cytomegaloviruses (CMVs) are highly prevalent, persistent human pathogens that not only evade but also shape our immune responses. Natural killer (NK) cells play an important role in the control of CMV and CMVs have in turn developed a plethora of immunoevasion mechanisms targeting NK cells. This complex interplay can leave a long-lasting imprint on the immune system in general and affect responses towards other pathogens and vaccines. This review aims to provide an overview of NK cell biology and development, the manipulation of NK cells by CMVs and the potential impact of these evasion strategies on responses to vaccination...
September 27, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28960280/functional-specialization-of-intestinal-dendritic-cell-subsets-during-th2-helminth-infection-in-mice
#19
Stephen A Redpath, Graham A Heieis, Lisa A Reynolds, Nicolette M Fonseca, Sandra S-Y Kim, Georgia Perona-Wright
Dendritic cells (DCs) are essential in dictating the nature and effectiveness of immune responses. In the intestine DCs can be separated into discrete subsets, defined by expression of CD11b and CD103, each with different developmental requirements and distinct functional potential. Recent evidence has shown that different intestinal DC subsets are involved in the induction of T helper (Th)17 and regulatory T cell responses, but the cells that initiate Th2 immune responses are still incompletely understood...
September 27, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28952147/genetic-variation-of-human-neutrophil-fc%C3%AE-receptors-and-sirp%C3%AE-in-antibody-dependent-cellular-cytotoxicity-towards-cancer-cells
#20
Louise W Treffers, Xi Wen Zhao, Joris van der Heijden, Sietse Q Nagelkerke, Dieke J van Rees, Patricia Gonzalez, Judy Geissler, Paul Verkuijlen, Michel van Houdt, Martin de Boer, Taco W Kuijpers, Timo K van den Berg, Hanke L Matlung
The efficacy of cancer therapeutic antibodies varies considerably among patients. Anti-cancer antibodies act through different mechanisms, including antibody-dependent cellular cytotoxicity (ADCC) triggered via Fcγ receptors (FcγR). This phagocyte ADCC can be promoted by interference with CD47-SIRPα interactions, but the magnitude of this enhancement also varies among individuals. Both FcγR and SIRPα display considerable genetic variation, and we investigated whether this explains some of the variability in ADCC...
September 27, 2017: European Journal of Immunology
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