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European Journal of Immunology

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https://www.readbyqxmd.com/read/27910098/gata-3-specific-dnazyme-a-novel-approach-for-stratified-asthma-therapy
#1
REVIEW
Holger Garn, Harald Renz
It is now well established that type-2 immune mechanisms drive the inflammation in about 50% of asthma patients. The major cellular and molecular players regulating this important network have been identified. In terms of therapeutic intervention, cytokine and cytokine-receptor pathways have been given major attention, since these molecules are relatively easily accessible for a blockade through monoclonal antibodies, and a number of positive clinical results support this concept. However, targeting events controlling the type-2 immunity network upstream of selective cytokine pathways would be equally attractive...
December 2, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27891600/human-pdcs-display-sex-specific-differences-in-type-i-interferon-subtypes-and-interferon-%C3%AE-%C3%AE-receptor-expression
#2
Susanne Ziegler, Claudia Beisel, Kathrin Sutter, Morgane Griesbeck, Heike Hildebrandt, Sven Hagen, Ulf Dittmer, Marcus Altfeld
The outcomes of many diseases differ between women and men, with women experiencing a higher incidence and more severe pathogenesis of autoimmune and some infectious diseases. It has been suggested that this is partially due to activation of plasmacytoid dendritic cells (pDCs), the main producers of interferon (IFN)-α, in response to toll-like receptor (TLR) 7 stimulation. We investigated the induction of type I IFN (IFN-I) subtypes upon TLR7 stimulation on isolated pDCs. Our data revealed a sex-specific differential expression of IFN-Is, with pDCs from females showing a significantly higher mRNA expression of all 13 IFNα-subtypes...
November 28, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27891580/acute-infection-with-the-intestinal-parasite-trichuris-muris-has-long-term-consequences-on-mucosal-mast-cell-homeostasis-and-epithelial-integrity
#3
Daniel Sorobetea, Jacob Bak Holm, Henrietta Henningsson, Karsten Kristiansen, Marcus Svensson-Frej
A hallmark of parasite infection is the accumulation of innate immune cells, notably granulocytes and mast cells, at the site of infection. While this is typically viewed as a transient response, with the tissue returning to steady state once the infection is cleared, we found that mast cells accumulated in the large-intestinal epithelium following infection with the nematode Trichuris muris and persisted at this site for several months after worm expulsion. Mast cell accumulation in the epithelium was associated with the induction of type-2 immunity and appeared to be driven by increased maturation of local progenitors in the intestinal lamina propria...
November 28, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27883186/lactate-at-the-crossroads-of-metabolism-inflammation-and-autoimmunity
#4
Valentina Pucino, Michele Bombardieri, Costantino Pitzalis, Claudio Mauro
For a long time after its discovery at the beginning of the 20th century, lactate was considered a waste product of cellular metabolism. Starting in the early '90s, however, lactate has begun to be recognised as an active molecule capable of modulating the immune response. Inflammatory sites, including in rheumatoid arthritis synovitis, are characterised by the accumulation of lactate, which is partly responsible for the establishment of an acidic environment. We have recently reported that T cells sense lactate via the expression of specific transporters, leading to inhibition of their motility...
November 24, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27883180/mitochondrial-reactive-oxygen-species-suppress-humoral-immune-response-through-reduction-of-cd19-expression-in-b-cells-in-mice
#5
Masato Ogura, Takeshi Inoue, Junko Yamaki, Miwako K Homma, Tomohiro Kurosaki, Yoshimi Homma
Reactive oxygen species (ROS) are implicated in the modulation of diverse processes including immune responses. To evaluate the effects of metabolic ROS produced by mitochondria on B-cell function and development, we created transgenic (Tg) mice expressing a phosphorylation-defective mutant of succinate dehydrogenase A (SDHA(Y215F) ) in B cells (bSDHA(Y215F) ). Splenic B cells in male, but not female, bSDHA(Y215F) mice produced three times more ROS than those in the control mice, and had decreased production of IgM, IgG1 , and IgG3 , and affinity maturation of IgG1 against T-cell-dependent antigens...
November 24, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27873323/inflammation-enhances-the-vaccination-potential-of-cd40-activated-b-cells-in-mice
#6
Mélissa Mathieu, Livia Odagiu, Léa Gaudot, Jean-François Daudelin, Heather J Melichar, Réjean Lapointe, Nathalie Labrecque
Vaccination with antigen-pulsed CD40-activated B (CD40-B) cells can efficiently lead to the in vivo differentiation of naive CD8(+) T cells into fully functional effectors. In contrast to bone marrow-derived dendritic cell (BMDC) vaccination, CD40-B cell priming does not allow for memory CD8(+) T-cell generation but the reason for this deficiency is unknown. Here, we show that compared to BMDCs, murine CD40-B cells induce lower expression of several genes regulated by T-cell receptor signalling, co-stimulation and inflammation (signals 1 to 3) in mouse T cells...
November 22, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27873300/local-checkpoint-inhibition-of-ctla-4-as-a-monotherapy-or-in-combination-with-anti-pd1-prevents-the-growth-of-murine-bladder-cancer
#7
Luuk van Hooren, Linda C Sandin, Igor Moskalev, Peter Ellmark, Anna Dimberg, Peter Black, Thomas H Tötterman, Sara M Mangsbo
Checkpoint blockade of CTLA-4 results in long-lasting survival benefits in metastatic cancer patients. However, patients treated with CTLA-4 blockade have suffered from immune related adverse events, most likely due to the breadth of the induced T-cell activation. Here, we investigated the efficacy of a local low-dose anti-CTLA-4 administration for treatment of subcutaneous or orthotopic MB49 bladder carcinoma in C57BL/6 mice. When MB49 tumors were grown subcutaneously, peritumoral injection of anti-CTLA-4 treatment was equally effective as intravenous or subcutaneous (non-tumor bearing flank) administration...
November 22, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27859043/monocyte-derived-dendritic-cells-enhance-protection-against-secondary-influenza-challenge-by-controlling-the-switch-in-cd82-t-cell-immunodominance
#8
Jazmina L G Cruz, José V Pérez-Girón, Anja Lüdtke, Sergio Gómez-Medina, Paula Ruibal, Juliana Idoyaga, César Muñoz-Fontela
Influenza virus infection triggers an increase in the number of monocyte-derived dendritic cells (moDCs) in the respiratory tract, but the role of these cells during antiviral immunity is still unclear. Here we show that during influenza infection, moDCs dominate the late activation of CD8(+) T cells and trigger the switch in immunodominance of the CD8(+) T-cell response from acidic polymerase (PA)-specificity to nucleoprotein (NP)-specificity. Abrogation of monocyte recruitment or depletion of moDCs strongly compromised host resistance to secondary influenza challenge...
November 18, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27859047/human-b-cell-memory-is-shaped-by-age-and-tissue-specific-t-independent-and-gc-dependent-events
#9
A Aranburu, E Piano Mortari, A Baban, E Giorda, S Cascioli, V Marcellini, M Scarsella, S Ceccarelli, S Corbelli, N Cantarutti, R De Vito, A Inserra, L Nicolosi, A Lanfranchi, F Porta, C Cancrini, A Finocchi, R Carsetti
Switched and IgM memory B cells execute different and non-interchangeable functions. We studied memory B cells in children of different ages, in peripheral blood and spleen and compared them with those of children born asplenic or unable to build germinal centers. We show that, whereas switched memory B cells are mostly generated in the germinal centers at all ages, IgM memory B cells can be distinct in three types with different developmental history. Innate IgM memory B cells, the largest pool in infants, are generated in the spleen by a germinal center-independent mechanism...
November 16, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27861808/peptidomic-analysis-of-type-1-diabetes-associated-hla-dq-molecules-and-the-impact-of-hla-dm-on-peptide-repertoire-editing
#10
Zemin Zhou, Eduardo Reyes-Vargas, Hernando Escobar, Kuan Y Chang, Adam P Barker, Alan L Rockwood, Julio C Delgado, Xiao He, Peter E Jensen
HLA-DM and class II associated invariant chain (Ii) are key cofactors in the MHC class II (MHCII) antigen processing pathway. We used tandem mass spectrometry sequencing to directly interrogate the global impact of DM and Ii on the repertoire of MHCII-bound peptides in human embryonic kidney 293T cells expressing HLA-DQ molecules in the absence or presence of these cofactors. Ii and DM have a major impact on the repertoire of peptides presented by DQ1 and DQ6, with the caveat that this technology is not quantitative...
November 15, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27859053/b-cell-intrinsic-function-of-tapp-adaptors-in-controlling-germinal-center-responses-and-autoantibody-production-in-mice
#11
Nipun Jayachandran, Ivan Landego, Sen Hou, Dario R Alessi, Aaron J Marshall
Control of B-cell signal transduction is critical to prevent production of pathological autoantibodies. Tandem PH domain containing proteins (TAPPs) specifically bind PI(3,4)P2, a phosphoinositide product generated by PI 3-kinases and the phosphatase SHIP. TAPP KI mice bearing PH domain-inactivating mutations in both TAPP1 and TAPP2 genes, uncoupling them from PI(3,4)P2, exhibit increased BCR-induced activation of the kinase Akt and develop lupus-like characteristics including anti-DNA antibodies and deposition of immune complexes in kidneys...
November 15, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27861804/cd103-cd11b-salivary-gland-dendritic-cells-have-antigen-cross-presenting-capacity
#12
Lu Lu, Yukinori Tanaka, Naoto Ishii, Takashi Sasano, Shunji Sugawara
Dendritic cells (DCs) in lymphoid and non-lymphoid tissues are professional antigen-presenting cells that are essential for effective immunity and tolerance. However, the presence and characteristics of DCs in steady-state salivary glands (SGs) currently remain unknown. We herein identified CD64(-) CD11c(+) classical DCs (cDCs) as well as CD64(+) macrophages among CD45(+) MHC class II(+) antigen-presenting cells in steady-state murine SGs. SG cDCs were divided into CD103(+) CD11b(-) and CD103(-) CD11b(+) cDCs...
November 11, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27861803/%C3%AE-4-%C3%AE-1-integrin-promotes-accumulation-of-tissue-resident-memory-cd8-t-cells-in-salivary-glands
#13
Sandra Woyciechowski, Maike Hofmann, Hanspeter Pircher
The salivary glands (SGs) of virus-immune mice contain substantial numbers of tissue-resident memory CD8(+) T cells (TRM cells) that can provide immunity to local infections. Integrins regulate entry of activated T cells into non-lymphoid tissues but the molecules that mediate migration of virus-specific CD8(+) T cells to the SGs have not yet been defined. Here, we found that polyinosinic-polycytidylic acid (poly(I:C)) strongly promoted the accumulation of P14 TCR-transgenic CD8(+) TRM cells in SGs in an α4 β1 integrin-dependent manner...
November 11, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27861815/intestinal-helminth-infection-induces-highly-functional-resident-memory-cd4-t-cells-in-mice
#14
Svenja Steinfelder, Sebastian Rausch, Dörte Michael, Anja A Kühl, Susanne Hartmann
Immunity to intestinal nematodes requires CD4⁺ Th2-cell responses, including IL-4 and IL-13 production. Chronic infection with intestinal nematodes leads to downregulation of these responses, and few functional T helper (Th) 2 cells are detected in secondary lymphoid organs in the chronic phase or after abrogation of infection. Here, we show with a natural murine infection with Heligmosomoides polygyrus that highly functional memory Th2 cells persist in the lamina propria and in addition in the peritoneal cavity (PC) after abrogation of infection...
November 10, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27861809/immune-monitoring-in-renal-transplantation-the-search-for-biomarkers
#15
Richard Danger, Birgit Sawitzki, Sophie Brouard
It is now widely accepted that in order to improve long-term graft function and survival, a more personalized immunosuppressive treatment of transplant patients according to the individual anti-donor immune response status is needed. This applies to the identification of potentially "high-risk" patients likely to develop acute rejection episodes or display an accelerated decline of graft function, patients who might need immunosuppression intensification, and operationally tolerant patients suitable for immunosuppression minimization or weaning off...
November 10, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27861793/a-novel-foxn1-egfp-mouse-model-identifies-bmp4-induced-maintenance-of-foxn1-expression-and-thymic-epithelial-progenitor-populations
#16
Marco Barsanti, Joanna M C Lim, Michael L Hun, Natalie Lister, Kahlia Wong, Maree V Hammett, Ailin Lepletier, Richard L Boyd, Antonietta Giudice, Ann P Chidgey
Although forkhead-box n1 (Foxn1) is a critical thymic epithelial cell regulator in thymus organogenesis, its association with epithelial differentiation and homeostasis in the postnatal and aged thymic microenvironment remains conflicting. Consequently, we have generated a Foxn1(eGFP/+) knock-in mouse model that allows for refined investigation of the aging thymic epithelium. This reporter line differs from those previously published in that concomitant expression of enhanced green fluorescent protein enables live cell sorting of Foxn1(+) cell populations...
November 10, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27859042/hla-g-promotes-myeloid-derived-suppressor-cell-mdsc-accumulation-and-suppressive-activity-during-human-pregnancy-through-engagement-of-the-receptor-ilt4
#17
Natascha Köstlin, Anna-Lena Ostermeir, Bärbel Spring, Julian Schwarz, Alexander Marmé, Christina B Walter, Christian F Poets, Christian Gille
Establishing and maintaining maternal-fetal tolerance is essential for a successful pregnancy; failure of immunological adaptation to pregnancy leads to severe complications such as abortion or preterm delivery. Myeloid-derived suppressor cells (MDSCs) are innate immune cells that suppress T-cell responses, expand during pregnancy and thus may play a role in tolerance induction. Human leucocyte antigen G (HLA-G) is a major histocompatibility complex (MHC) I molecule with immune-modulatory properties, which is expressed during pregnancy...
November 10, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27861791/foxp1-is-a-key-regulator-of-quiescence-in-healthy-human-cd3-cd4-t-cells-and-is-constitutively-repressed-in-cd3-cd4-t-cells-from-patients-with-lymphoproliferative-disorders
#18
Soizic Garaud, Florence Roufosse, Pushpamali De Silva, Chunyan Gu-Trantien, Jean-Nicolas Lodewyckx, Hugues Duvillier, Sarah Dedeurwaerder, Martin Bizet, Matthieu Defrance, François Fuks, Françoise Bex, Karen Willard-Gallo
The forkhead box P1 (FOXP1) transcription factor has been shown to regulate the generation and maintenance of quiescent naïve murine T cells. In humans, FOXP1 expression has been correlated with overall survival in patients with peripheral T-cell lymphoma (PTCL), although its regulatory role in T-cell function is currently unknown. We found that FOXP1 is normally expressed in all human leukocyte subpopulations. Focusing on primary human CD4(+) T cells, we show that nuclear expression of FOXP1 predominates in naïve cells with significant downregulation detected in memory cells from blood and tonsils...
November 8, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27861788/phenotypically-resembling-myeloid-derived-suppressor-cells-are-increased-in-children-with-hiv-and-exposed-infected-with-mycobacterium-tuberculosis
#19
Nelita Du Plessis, Ruschca Jacobs, Andrea Gutschmidt, Zhuo Fang, Paul D van Helden, Manfred B Lutz, Anneke C Hesseling, Gerhard Walzl
Increased disease susceptibility during early life has been linked to immune immaturity, regulatory T-cell/TH2 immune biasing and hyporesponsiveness. The contribution of myeloid derived suppressor cells (MDSCs) remains uninvestigated. Here, we assessed peripheral MDSC in HIV-infected and -uninfected children with tuberculosis (TB) disease before, during and after TB treatment, along with matched household contacts (HHCs), HIV-exposed, -infected and -uninfected children without recent TB exposure. Serum analytes and enzymes associated with MDSC accumulation/activation/function were measured by colorimetric- and fluorescence arrays...
November 8, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27859048/%C3%AE-cell-specific-il-35-therapy-suppresses-ongoing-autoimmune-diabetes-in-nod-mice
#20
Fatima Manzoor, Mark C Johnson, Chengwen Li, R Jude Samulski, Bo Wang, Roland Tisch
IL-35 is a recently identified cytokine exhibiting potent immunosuppressive properties. The therapeutic potential and effects of IL-35 on pathogenic T effector (Teff) cells and Foxp3(+) Treg cells, however, are ill-defined. We tested the capacity of IL-35 to suppress ongoing autoimmunity in NOD mice. For this purpose, an adeno-associated virus vector in which IL-35 transgene expression is selectively targeted to β cells via an insulin promoter (AAV8mIP-IL35) was used. AAV8mIP-IL35 vaccination of NOD mice at a late preclinical stage of type 1 diabetes (T1D) suppressed β-cell autoimmunity and prevented diabetes onset...
November 8, 2016: European Journal of Immunology
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