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European Journal of Immunology

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https://www.readbyqxmd.com/read/29349774/the-vaccine-adjuvant-alum-promotes-il-10-production-that-suppresses-th1-responses
#1
Ewa Oleszycka, Sean McCluskey, Fiona A Sharp, Natalia Muñoz-Wolf, Emily Hams, Aoife L Gorman, Padraic G Fallon, Ed C Lavelle
The effectiveness of many vaccines licensed for clinical use relates to the induction of neutralising antibodies, facilitated by the inclusion of vaccine adjuvants, particularly alum. However, the ability of alum to preferentially promote humoral rather than cellular, particularly Th1-type responses, is not well understood. We demonstrate that alum activates immunosuppressive mechanisms following vaccination, which limit its capacity to induce Th1 responses. One of the key cytokines limiting excessive immune responses is IL-10...
January 19, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29336030/the-aryl-hydrocarbon-receptor-modulates-the-function-of-human-cd56bright-nk-cells
#2
Uriel Y Moreno-Nieves, David C Mundy, June Ho Shin, Kenric Tam, John B Sunwoo
Human natural killer (NK) cells are divided into two subsets: CD56bright and CD56dim NK cells, which differ in maturation, function and distribution. Mechanisms regulating NK cell functions are not completely understood. Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, that binds to a variety of endogenous and exogenous molecules, and that has recently been shown to modulate the function and differentiation of immune cells. Here, we studied the expression of AhR and its involvement in the regulation of NK cell functions...
January 16, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29331106/kbtbd2-inhibits-the-cytotoxic-activity-of-immortalized-nk-cells-through-down-regulating-mtor-signaling-in-a-mouse-hepatocellular-carcinoma-model
#3
Kai Dai, Yabing Huang, Zubing Chen, Xiaomei Sun, Lihua Yang, Yingan Jiang
Natural killer cell (NK cell)-based immunotherapy is a promising therapeutic strategy for hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying the regulation of NK cell function in the tumor sites are not completely elucidated. In this study, we identified the enhanced expression of kelch repeat and BTB (POZ) domain containing 2 (Kbtbd2) in intratumoral NK cells in a mouse HCC implantation model as a negative regulator of NK cells. To investigate this interaction,, we used a Tet-on inducible expression system to control Kbtbd2 expression in an immortalized mouse NK cell line KIL C...
January 13, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29318612/transplanted-human-thymus-slices-induce-and-support-t-cell-development-in-mice-after-cryopreservation
#4
Susan Ross, Melissa Cheung, Ching-In Lau, Neil Sebire, Michael Burch, Peter Kilbride, Barry Fuller, G John Morris, E Graham Davies, Tessa Crompton
Here we show that slices of human thymus tissue that have been frozen and thawed can induce and support T-cell development when transplanted into nude mice. Babies born without a thymus require urgent treatment to reconstitute T-cell immunity. Thymus tissue is removed from infants during cardiac surgery, to allow access to the heart. This discarded thymus tissue can be transplanted into athymic infants to reconstitute T-cell immunity. Slices of thymus tissue are transplanted into the thigh, after a two-three week culture period to deplete thymocytes...
January 10, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29315532/treatment-of-mcpt8dtr-mice-with-high-or-low-dose-diphtheria-toxin-leads-to-differential-depletion-of-basophils-and-granulocyte-macrophage-progenitors
#5
Carole El Hachem, Pierre Hener, Peggy Kirstetter, Jiagui Li, Susan Chan, Mei Li
Basophils have been recently recognized to play important roles in type 2 immune responses during allergies and parasitic infection, largely due to the development of novel tools for the in vivo study of these cells. As such, the genetically-engineered MCPT8DTR mouse line has been used to specifically deplete basophils following treatment with diphtheria toxin (DT). In this study, we showed that DT-injected MCPT8DTR mice exhibited a striking decrease of eosinophils and neutrophils in skin when subjected to a hapten fluorescein isothiocyanate (FITC)-induced allergic contact dermatitis (ACD) experimental protocol...
January 8, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29315518/hyaluronan-binding-by-cd44-reduces-the-memory-potential-of-activated-murine-cd8-t-cells
#6
Sally S M Lee-Sayer, Nina Maeshima, Meghan N Dougan, Anita Dahiya, Arif A Arif, Manisha Dosanjh, Christopher A Maxwell, Pauline Johnson
Expansion and death of effector CD8 T cells are regulated to limit immunopathology and cells that escape contraction go on to generate immunological memory. CD44, a receptor for the extracellular matrix component hyaluronan, is a marker of activated and memory T cells. Here, we show with a murine model that the increase in CD44 expression and hyaluronan binding induced upon CD8 T cell activation was proportional to the strength of TCR engagement, thereby identifying the most strongly activated T cells. When CD44-/- and CD44+/+ OT-I CD8 T cells were adoptively transferred into mice challenged with Listeria-OVA, there was a slight increase in the percentage of CD44+/+ cells at the effector site...
January 8, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29313961/impaired-phagocytosis-directs-human-monocyte-activation-in-response-to-fungal-derived-%C3%AE-glucan-particles
#7
Giorgio Camilli, Elif Eren, David L Williams, Vishukumar Aimanianda, Etienne Meunier, Jessica Quintin
Recognition of the fungal cell wall carbohydrate β-glucan by the host receptor Dectin-1 elicits broad immunomodulatory responses, such as phagocytosis and activation of oxidative burst. These responses are essential for engulfing and killing fungal pathogens. Phagocytic monocytes are key mediators of these early host inflammatory responses to infection. Remarkably, whether phagocytosis of fungal β-glucan leads to an inflammatory response in human monocytes remains to be established. Here, we show that phagocytosis of heat-killed Candida albicans is essential to trigger inflammation and cytokine release...
January 5, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29313959/cardiolipin-activates-antigen-presenting-cells-via-tlr2-pi3k-pkn1-akt-p38-nf-kb-signaling-to-prime-antigen-specific-na%C3%A3-ve-t-cells-in-mice
#8
Jung-Ah Cho, Tae-Joo Kim, Hye-Jung Moon, Young-Joo Kim, Hye-Kyung Yoon, Seung-Yong Seong
Mitochondrial defects and anti-mitochondrial cardiolipin (CL) antibodies are frequently detected in autoimmune disease patients. CL from dysregulated mitochondria activates various pattern recognition receptors, such as NLRP3. However, the mechanism by which mitochondrial CL activates antigen-presenting cells (APCs) as a damage-associated molecular pattern to prime antigen-specific naïve T cells, which is crucial for T-cell-dependent anti-cardiolipin IgG antibody production in autoimmune diseases is unelucidated...
January 4, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29293266/med1-deficiency-alters-the-somatic-hypermutation-spectrum-in-murine-b-cells
#9
LETTER
Léa Gaudot, Anne-Sophie Thomas-Claudepierre, Isabelle Robert, Ebe Schiavo, Vincent Heyer, Bernardo Reina-San-Martin
No abstract text is available yet for this article.
January 2, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29285761/aire-controls-the-recirculation-of-murine-foxp3-regulatory-t-cells-back-to-the-thymus
#10
Jennifer E Cowan, Song Baik, Nicholas I McCarthy, Sonia M Parnell, Andrea J White, William E Jenkinson, Graham Anderson
In the thymus, medullary thymic epithelial cells (mTEC) determine the fate of newly selected CD4+ and CD8+ single positive (SP) thymocytes. For example, mTEC expression of Aire controls intrathymic self-antigen availability for negative selection. Interestingly, alterations in both Foxp3+ Regulatory T-cells (T-Reg) and conventional SP thymocytes in Aire-/- mice suggest additional, yet poorly understood, roles for Aire during intrathymic T-cell development. To examine this, we analysed thymocytes from Aire-/- mice using Rag2GFP and Foxp3 expression, and a recently described CD69/MHCI subset definition of post-selection CD4+ conventional thymocytes...
December 29, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29283192/functional-and-phenotypical-analysis-of-il-6-secreting-cd4-t-cells-in-human-adipose-tissue
#11
Anja J de Jong, Sabrina Pollastro, Joanneke C Kwekkeboom, Stefan N Andersen, Annemarie L Dorjée, Aleida M Bakker, Fawaz Alzaid, Antoine Soprani, Rob G H H Nelissen, Jan B Mullers, Nicolas Venteclef, Niek de Vries, Margreet Kloppenburg, René E M Toes, Andreea Ioan-Facsinay
Emerging evidence indicates that a dynamic interplay between the immune system and adipocytes contributes to the disturbed homeostasis in adipose tissue of obese subjects. Recently, we observed IL-6-secretion by CD4+ T cells from the stromal vascular fraction (SVF) of the infrapatellar fat pad (IFP) of knee osteoarthritis patients directly ex vivo. Here we show that human IL-6+ CD4+ T cells from SVF display a more activated phenotype than the IL-6- T cells, as evidenced by the expression of the activation marker CD69...
December 28, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29282719/il-12-il-18-preactivated-donor-nk-cells-enhance-gvl-effects-and-mitigate-gvhd-after-allogeneic-hematopoietic-stem-cell-transplantation
#12
Yuan Song, Bo Hu, Yonghao Liu, Ziqi Jin, Yinsheng Zhang, Dandan Lin, Ying Zhu, Lei Lei, Huanle Gong, Yu Mei, Huey Yee Teo, Depei Wu, Haiyan Liu
Adoptive transfer of donor NK cells has the potential of mediating graft-versus-leukemia (GVL) effect while suppressing acute graft-versus-host-disease (aGVHD) during allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, these beneficial effects are limited by the transient function of adoptively transferred NK cells. Previous studies demonstrate that cytokine-induced memory-like NK cells that are preactivated by IL-12, IL-15, and IL-18 have enhanced effector functions and long life span in vivo...
December 27, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29280140/pkc%C3%AE%C2%B5%C3%A2-promotes-human-th17-differentiation-implications-in-the-pathophysiology-of-psoriasis
#13
Silvia Martini, Giulia Pozzi, Cecilia Carubbi, Elena Masselli, Daniela Galli, Sergio Di Nuzzo, Antonio Banchini, Giuliana Gobbi, Marco Vitale, Prisco Mirandola
PKCε is implicated in T cell activation and proliferation and is overexpressed in CD4+ -T cells from patients with autoimmune Hashimoto's Thyroiditis. Although this might induce the suspicion that PKCε takes part in autoimmunity, its role in the molecular pathophysiology of immune-mediated disorders is still largely unknown. We studied PKCε expression in circulating CD4+ -T cells from patients with Psoriasis, a skin disorder characterized by an increased amount of Th17 cells, a CD4+ subset that is critical in the development of autoimmunity...
December 27, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29277896/c5ar-activation-in-the-absence-of-c5a-a-new-disease-mechanism-of-autoimmune-hemolytic-anemia-in-mice
#14
Shahzad N Syed, Eduard Rau, Mareen Ziegelmann, Georgios Sogkas, Bernhard Brüne, Reinhold E Schmidt
IgG Fc receptors (FcγRs) and the C5a anaphylatoxin receptor (C5aR) were identified as key regulators of type II autoimmune injury in mice. However, and with respect to C5aR, the relative importance of C5a for IgG autoantibody-induced cellular destruction remained unclear. Using an experimental model of autoimmune hemolytic anemia (AIHA), we here report marked differences in the development of AIHA between mice lacking C5aR and C5-deficient (Hc0 ) strain, indicating a limited role of C5 in this type of C5aR-regulated disease...
December 25, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29274245/the-gasdermin-d-pore-acts-as-a-conduit-for-il-1%C3%AE-secretion-in-mice
#15
Rosalie Heilig, Mathias S Dick, Lorenzo Sborgi, Etienne Meunier, Sebastian Hiller, Petr Broz
The pro-inflammatory cytokine IL-1β is well known for its role in host defense and the initiation of potent inflammatory responses. It is processed from its inactive pro-form by the inflammatory caspase-1 into its mature bioactive form, which is then released from the cell via an unconventional secretion mechanism. Recently, gasdermin-D has been identified as a new target of caspase-1. After proteolytical cleavage of gasdermin-D, the N-terminal fragment induces pyroptosis, a lytic cell death, by forming large permeability pores in the plasma membrane...
December 23, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29272036/adaptive-immune-response-to-clostridium-difficile-infection-a-perspective-for-prevention-and-therapy
#16
REVIEW
William D Rees, Theodore S Steiner
Clostridium difficile infection (CDI) is one of the most important nosocomial illnesses and a major cause of morbidity and mortality. While initial treatment of CDI is usually successful, unprovoked relapses remain an important and frustrating problem. This review examines the literature describing the natural immune response to CDI, and to what extent it can explain the propensity for relapses. In particular, we discuss studies on antibody and, to a lesser extent, B cell and T cell responses in CDI. Despite years of study, there remains incomplete understanding of the natural antibody response to the major pathogenic toxins, TcdA and TcdB, and other bacterial antigens, in CDI...
December 22, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29266251/siglec-1-inhibits-rsv-induced-interferon-gamma-production-by-adult-t-cells-in-contrast-to-newborn-t-cells
#17
Jop Jans, Wendy W J Unger, Marloes Vissers, Inge M L Ahout, Inge Schreurs, Arthur Wickenhagen, Ronald de Groot, Marien I de Jonge, Gerben Ferwerda
Interferon gamma (IFN-γ) plays an important role in the antiviral immune response during respiratory syncytial virus (RSV) infections. Monocytes and T cells are recruited to the site of RSV infection, but it is unclear whether cell-cell interactions between monocytes and T cells regulate IFN-γ production. In this study, micro-array data identified the upregulation of sialic acid-binding immunoglobulin-type lectin 1 (Siglec-1) in human RSV-infected infants. In vitro, RSV increased expression of Siglec-1 on healthy newborn and adult monocytes...
December 20, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29266242/age-associated%C3%A2-b-cells-expanded-in-autoimmune-mice-are-memory-cells-sharing-h-cdr3-selected-repertoires
#18
Alaitz Aranburu, Nina Höök, Natalija Gerasimcik, Bjorn Corleis, Weicheng Ren, Alessandro Camponeschi, Hans Carlsten, Ola Grimsholm, Inga-Lill Mårtensson
Age-associated B cells (ABCs) represent a distinct cell population expressing low levels of CD21 (CD21-/low ). The Ig repertoire expressed by ABCs in aged mice is diverse and exhibits signs of somatic hypermutation (SHM). A CD21-/low B-cell population is expanded in autoimmune diseases, e.g. systemic lupus erythematosus, as well as in lupus-prone NZB/W mice and in mice lacking a pre-B cell receptor (SLC-/- ). However, the nature of the CD21-/low B cells (hereafter ABCs) in autoimmunity is not well understood...
December 19, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29251774/altered-toll-like-receptor-responsiveness-underlies-a-dominant-heritable-defect-in-b-cell-tolerance-in-autoimmune-new-zealand-black-mice
#19
Amy G Clark, Elizabeth S Buckley, Mary H Foster
Systemic lupus erythematosus is a debilitating autoimmune disease in which autoantibodies and autoreactive T cells destroy kidneys and other organs. Disease is clinically and genetically heterogeneous, suggesting that underlying mechanisms vary between patients. We previously used an autoantibody transgenic mouse reporter system to examine the effect of different autoimmune backgrounds on B-cell tolerance, failure of which is a fundamental defect in lupus. We identified a defect consistent with reversible anergy induced by endotoxin stimulation of B cells from Ig transgenic New Zealand Black (NZB) mice...
December 18, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29244204/respiratory-viral-infections-and-atopic-development-from-possible-mechanisms-to-advances-in-treatment
#20
REVIEW
Lisa M Martorano, Mitchell H Grayson
Atopic sensitization and allergic diseases are increasing in modernized countries. These diseases affect millions of individuals, but the mechanisms behind their development are not fully understood. One hypothesis relates to early life respiratory viral infections driving the development of atopic disease including asthma. This review presents the current state of the field, focusing on epidemiologic data supporting a role for early life respiratory viruses in the development of specific IgE, both against aeroallergens and the respiratory virus...
December 15, 2017: European Journal of Immunology
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