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European Journal of Immunology

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https://www.readbyqxmd.com/read/28318017/thymic-crosstalk-restrains-the-pool-of-cortical-thymic-epithelial-cells-with-progenitor-properties
#1
Catarina Meireles, Ana R Ribeiro, Rute D Pinto, Catarina Leitão, Pedro M Rodrigues, Nuno L Alves
Cortical (cTEC) and medullary (mTEC) thymic epithelial cells establish key microenvironments for T-cell differentiation and arise from thymic epithelial cell progenitors (TEP). However, the nature of TEPs and the mechanism controlling their stemness in the postnatal thymus remain poorly defined. Using TEC clonogenic assays as a surrogate to survey TEP activity, we found that a fraction of cTECs generates specialized clonal-derived colonies, which contain cells with sustained colony-forming capacity (ClonoTECs)...
March 20, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28303575/isoform-localization-of-dectin-1-regulates-the-signaling-quality-of-anti-fungal-immunity
#2
Mike Fischer, Jörg P Müller, Bärbel Spies-Weisshart, Christine Gräfe, Oliver Kurzai, Kerstin Hünniger, Andreas Hochhaus, Sebastian Scholl, Ulf Schnetzke
Dectin-1 is recognized as a major receptor for fungal ß-glucans and contributes to anti-fungal immunity. Human monocyte populations express Dectin-1 isoforms A and B, which differ by the presence of a stalk region and its N-linked glycosylation site. Here, we analyzed the expression of both isoforms in human monocyte-derived cells. The cellular localization on cell lines stably expressing either Dectin-1 isoform A or B was studied by flow cytometry and confocal laser scanning microscopy. Intracellular protein signaling and cytokine production was analyzed by immunoblotting and cytometric bead arrays, respectively...
March 16, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28301039/bach2-regulates-aid-mediated-immunoglobulin-gene-conversion-and-somatic-hypermutation-in-dt40-b-cells
#3
Paulina M Budzyńska, Minna K Kyläniemi, Teemu Kallonen, Anni I Soikkeli, Kalle-Pekka Nera, Olli Lassila, Jukka Alinikula
The transcription factor Bach2 is required for germinal centre formation, somatic hypermutation (SHM) and class-switch recombination (CSR) of immunoglobulins. SHM and CSR are initiated by activation-induced cytidine deaminase (AID) which has potential to induce human B cell lymphoma. To understand the role of Bach2 in AID-mediated immunoglobulin gene diversification processes, we established a BACH2-deficient DT40 B cell line. We show that in addition to allowing SHM, Bach2 drives immunoglobulin gene conversion (GCV), another AID-dependent antibody gene diversification process...
March 16, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28299776/toll-like-receptors-elicit-different-recruitment-kinetics-of-monocytes-and-neutrophils-in-mouse-acute-inflammation
#4
Beat A Imhof, Stephane Jemelin, Yalin Emre
Leukocyte recruitment is an important process in combatting pathogens. The largest class of circulating leukocytes are neutrophils, which rapidly invade inflamed tissue, followed by inflammatory Ly6C(+) monocytes. Ly6C(low) monocytes patrol the endothelial wall routinely in the steady state. We recently reported early luminal recruitment of Ly6C(low) monocytes, which preceded and orchestrated neutrophil arrival and extravasation in response to TLR7/8-mediated vascular inflammation. Here we dissected the kinetics of recruitment of monocytes and neutrophils and examined the dynamics of Ly6C(low) monocytes in response to several other Toll-like receptor (TLR) agonists, using intravital confocal microscopy...
March 16, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28295300/ifn-%C3%AE-directly-inhibits-murine-b-cell-precursor-leukemia-initiating-cell-proliferation-early-in-life
#5
Mario Fidanza, Alix E Seif, Sumin Jo, Amina Kariminia, Nina Rolf, Laura M Sly, Stephan A Grupp, Gregor S D Reid
The early-life immune environment has been implicated as a modulator of acute lymphoblastic leukemia (ALL) development in children, with infection being associated with significant changes in ALL risk. Furthermore, polymorphisms in several cytokine genes, including IL-10 and IFN-γ, are associated with leukemia development. However, the mechanisms and timing of these influences remain unknown. Here, we use the Eμ-ret transgenic mouse model of B-cell precursor ALL to assess the influence of IFN-γ on the early-life burden of leukemia-initiating cells...
March 15, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28295238/il-17-and-il-22-in-immunity-driving-protection-and-pathology
#6
REVIEW
Eyerich Kilian, Dimartino Valentina, Cavani Andrea
IL-17 and IL-22 are tissue-signaling cytokines that favor protection and regeneration of barrier organs such as the skin, lung, and gastrointestinal system. Both cytokines share cellular sources, signaling pathways, and functional aspects; however, taking a closer look they differ, e.g. in their pro-inflammatory or regenerative potential. A dysbalance of the carefully orchestrated tissue-signaling system might result in autoimmune diseases, promote cancer growth, or predispose to infectious diseases. This review highlights recent understandings in cellular sources, signaling mechanisms, physiologic as well as pathogenic role of the double-faceted cytokines IL-17 and IL-22...
March 15, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28295233/retention-of-ag-specific-memory-cd4-t-cells-in-the-draining-lymph-node-indicates-lymphoid-tissue-resident-memory-populations
#7
Clare L Marriott, Emma E Dutton, Michio Tomura, David R Withers
Several different memory T-cell populations have now been described based upon surface receptor expression and migratory capabilities. Here we have assessed murine endogenous memory CD4(+) T cells generated within a draining lymph node and their subsequent migration to other secondary lymphoid tissues. Having established a model response targeting a specific peripheral lymph node, we temporally labelled all the cells within draining lymph node using photoconversion. Tracking of photoconverted and non-photoconverted Ag-specific CD4(+) T cells revealed the rapid establishment of a circulating memory population in all lymph nodes within days of immunisation...
March 15, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28295265/card9-controls-dectin-1-induced-t-cell-cytotoxicity-and-tumor-growth-in-mice
#8
Haas Tobias, Heidegger Simon, Wintges Alexander, Bscheider Michael, Bek Sarah, Fischer Julius C, Eisenkolb Gabriel, Schmickl Martina, Spoerl Silvia, Peschel Christian, Poeck Hendrik, Ruland Jürgen
Activation of the C-type lectin receptor Dectin-1 by β-glucans triggers multiple signals within dendritic cells (DCs) that result in activation of innate immunity. While these mechanisms can potently prime CD8(+) cytotoxic T cell (CTL) responses without additional adjuvants, the Dectin-1 effector pathways that control CTL induction remain unclear. Here we demonstrate that Dectin-1-induced CTL cross-priming in mice does not require inflammasome activation but strictly depends on the adapter protein Card9 in vitro...
March 10, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28295231/deficiency-in-irak4-activity-attenuates-manifestations-of-murine-lupus
#9
Michael Murphy, Goutham Pattabiraman, Tissa T Manavalan, Andrei E Medvedev
Interleukin-1 receptor-associated kinase (IRAK) 4 mediates host defense against infections. As an active kinase, IRAK4 elicits full spectra of myeloid differentiation primary response protein (MyD) 88-dependent responses, while kinase-inactive IRAK4 induces a subset of cytokines and negative regulators whose expression is not regulated by mRNA stability. IRAK4 kinase activity is critical for resistance against Streptococcus pneumonia, but its involvement in autoimmunity is incompletely understood. In this study, we determined the role of IRAK4 kinase activity in murine lupus...
March 10, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28295230/microvesicles-released-by-apoptotic-human-neutrophils-suppress-proliferation-and-il-2-il-2-receptor-expression-of-resting-t-helper-cells
#10
Guifen Shen, Stefan Krienke, Petra Schiller, Anna Nießen, Susanne Neu, Volker Eckstein, Martin Schiller, Hanns-Martin Lorenz, Lars-Oliver Tykocinski
Membrane-coated microvesicles (MVs) have been identified as important mediators in intercellular communication. During the process of apoptosis, dying cells dynamically release MVs. Neutrophils are the most abundant type of leukocytes in the circulation. Due to their very short lifespan, it is likely that they are the source of large amounts of apoptotic cell-derived MVs. Here, we show that MVs released by apoptotic human polymorphonuclear neutrophils (apoPMN-MVs), but not the apoptotic neutrophils themselves, selectively suppress the proliferation of CD25 (IL-2Rα)(neg) CD127 (IL-7Rα)(pos) Th cells in a dose-dependent manner...
March 10, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28295214/negative-regulators-of-the-rig-i-like-receptor-signaling-pathway
#11
REVIEW
Kendra M Quicke, Michael S Diamond, Mehul S Suthar
Upon recognition of specific molecular patterns on microbes, host cells trigger an innate immune response, which culminates in the production of type I interferons (IFNs), pro-inflammatory cytokines and chemokines, and restricts pathogen replication and spread within the host. At each stage of this response, there are stimulatory and inhibitory signals that regulate the magnitude, quality, and character of the response. Positive regulation promotes an antiviral state to control and eventually clear infection, whereas negative regulation dampens inflammation and prevents immune-mediated tissue damage...
March 10, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28294319/grpr-antagonist-protects-from-drug-induced-liver-injury-by-impairing-neutrophil-chemotaxis-and-motility
#12
Rafael S Czepielewski, Natália Jaeger, Pedro E Marques, Maísa M Antunes, Maurício M Rigo, Débora M Alvarenga, Rafaela V Pereira, Rodrigo D da Silva, Tiago G Lopes, Vinícius D da Silva, Bárbara N Porto, Gustavo B Menezes, Cristina Bonorino
Drug-induced liver injury (DILI) is a major cause of acute liver failure (ALF), where hepatocyte necrotic products trigger liver inflammation, release of CXCR2 ligands (IL-8) and other neutrophil chemotactic molecules. Liver infiltration by neutrophils is a major cause of the life threatening tissue damage that ensues. A GRPR (gastrin-releasing peptide receptor) antagonist impairs IL-8-induced neutrophil chemotaxis in vitro. We investigated its potential to reduce acetaminophen-induced ALF, neutrophil migration and mechanisms underlying this phenomenon...
March 10, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28294314/generation-of-precursor-immature-and-mature-murine-b1-cell-lines-from-c-myc-bcl-xl-overexpressing-pre-bi-cells
#13
Inge Wolf, Corinne Bouquet, Friederike Naumann, Fritz Melchers
Deregulated expression of c-myc and bcl-xL is long known to generate transformed B cells in humans and mice. We overexpressed these genes to induce in vitro and in vivo differentiation of fetal liver-derived mouse pre-BI cells to B1-lineage pre-BII-like, immature and mature B-cell lines and to Ig-secreting cells. In vitro, doxycycline-controlled c-myc/bcl-xL-overexpressing CD19(+) CD93(+) c-kikt(+) IgM(-) pre-BI cells differentiate to and survive as CD19(+) CD93(+) c-kit(-) IgM(+) immature B1 cells. Timed CpG-stimulation of these oncogene-overexpressing pre-B or immature B1 cells generates either CD19(+) CD93(low) c-kit(-) IgM(-) SLC(-) pre-BII-like, or IgM(+) MHCII(+) CD73(+) CD80(+) CD40(+) mature B1-cell lines and IgM-secreting B1 cells in vitro and fixes their state of differentiation...
March 10, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28276053/murine-thymic-nk-cells-are-distinct-from-ilc1s-and-have-unique-transcription-factor-requirements
#14
Sara Gabrielli, Mengxi Sun, April Bell, Erin C Zook, Renee F de Pooter, Loris Zamai, Barbara L Kee
Group 1 innate lymphoid cells include natural killer (NK) cells and ILC1s, which mediate the response to intracellular pathogens. Thymic NK (tNK) cells were described with hybrid features of immature NK cells and ILC1 but whether these cells are related to NK cells or ILC1 has not been fully investigated. We report that murine tNK cells expressed the NK-cell associated transcription factor EOMES and developed independent of the essential ILC1 factor TBET, confirming their placement within the NK lineage. Moreover, tNK cells resemble NK cells rather than ILC1 in their requirements for the E protein transcription factor inhibitor ID2...
March 9, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28271497/chronic-schistosomiasis-during-pregnancy-epigenetically-reprograms-t-cell-differentiation-in-offspring-of-infected-mothers
#15
Kathrin Klar, Sophie Perchermeier, Sonakshi Bhattacharjee, Hani Harb, Thure Adler, Rouzanna Istvanffy, Eva Loffredo-Verde, Robert Oostendorp, Harald Renz, Clarissa Prazeres da Costa
Schistosomiasis is a non-transplacental helminth infection. Chronic infection during pregnancy suppresses allergic airway responses in offspring. We addressed the question whether in utero exposure to chronic schistosome infection (Reg phase) in mice affects B cell and T cell development. Therefore, we focused our analysis on T cell differentiation capacity induced by epigenetic changes in promoter regions of signature cytokines in offspring. Here we show that naïve T cells from offspring of schistosome infected female mice had a strong capacity to differentiate into TH 1 cells, whereas TH 2 differentiation was impaired...
March 8, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28267207/listeria-monocytogenes-induces-an-interferon-enhanced-activation-of-the-integrated-stress-response-that-is-detrimental-for-resolution-of-infection-in-mice
#16
Carolina Valderrama, Amy Clark, Fumihiko Urano, Emil R Unanue, Javier A Carrero
Type I interferons (IFNs) induce a detrimental response during Listeria monocytogenes (L. monocytogenes) infection. We were interested in identifying mechanisms linking IFN signaling to negative host responses against L. monocytogenes infection. Herein we found that infection of myeloid cells with L. monocytogenes led to a coordinated induction of type I IFNs and activation of the integrated stress response (ISR). Infected cells did not induce Xbp1 splicing or BiP upregulation, indicating that the unfolded protein response was not triggered...
March 7, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28267197/taci-dependent-april-signaling-maintains-autoreactive-b-cells-in-a-mouse-model-of-systemic-lupus-erythematosus
#17
Ngoc Lan Tran, Pascal Schneider, Marie-Laure Santiago-Raber
Autoantibodies contribute to the development of Systemic Lupus Erythematosus (SLE). APRIL (a proliferation-inducing ligand), a member of the TNF superfamily, regulates plasma-cell survival and binds to TACI (transmembrane activator CAML interactor) and BCMA (B cell maturation antigen). We previously showed that APRIL blockade delayed disease onset in lupus-prone mice. In order to evaluate the role of APRIL receptors in the development of SLE, APRIL, TACI, BCMA or double TACI.BCMA null mutations were introduced into the Nba2...
March 7, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28266028/triggering-of-tlr-3-4-nod2-and-dc-sign-reduces-viral-replication-and-increases-t-cell-activation-capacity-of-hiv-infected-human-dendritic-cells
#18
Sylvain Cardinaud, Alejandra Urrutia, Angeline Rouers, Pierre-Grégoire Coulon, Jérome Kervevan, Clémence Richetta, Anne Bet, Emmanuel Atangana Maze, Martin Larsen, Maria-Candela Iglesias, Victor Appay, Stéphanie Graff-Dubois, Arnaud Moris
A variety of signals influence the capacity of dendritic cells (DCs) to mount potent antiviral cytotoxic T-cell (CTL) responses. In particular, innate immune sensing by pathogen recognition receptors (PRRs), such as TLR and C-type lectines, influences DC biology and affects their susceptibility to HIV infection. Yet, whether the combined effects of PPRs triggering and HIV infection influence HIV-specific CTL responses remain enigmatic. Here, we dissect the impact of innate immune sensing by PRRs on DC maturation, HIV infection and on the quality of HIV-specific CTL activation...
March 7, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28247911/opposing-effects-of-nrf2-and-nrf2-activating-compounds-on-the-nlrp3-inflammasome-independent-of-nrf2-mediated-gene-expression
#19
Martha Garstkiewicz, Gerhard E Strittmatter, Serena Grossi, Jennifer Sand, Gabriele Fenini, Sabine Werner, Lars E French, Hans-Dietmar Beer
The transcription factor Nrf2 regulates the expression of genes required for protection from xenobiotic and oxidative stress. Under normal conditions Nrf2 is constantly degraded upon ubiquitination, mediated by the Nrf2 inhibitor Keap1. Inflammasomes represent stress-induced protein complexes. They are critically involved in acute and chronic inflammation through caspase-1-mediated activation of pro-inflammatory cytokines. Here, we demonstrate that Nrf2 is as a positive regulator of the NLRP3 inflammasome. In contrast, Nrf2-activating compounds, including the anti-inflammatory drug dimethyl fumarate (DMF), inhibit inflammasome activation...
March 1, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28198545/the-therapeutic-t-cell-response-induced-by-tumor-delivery-of-tnf-and-melphalan-is-dependent-on-early-triggering-of-natural-killer-and-dendritic-cells
#20
Enrica Balza, Silvia Zanellato, Alessandro Poggi, Daniele Reverberi, Anna Rubartelli, Lorenzo Mortara
The fusion protein L19mTNF (mouse TNF and human antibody fragment L19 directed to fibronectin extra domain-B) selectively targets the tumor vasculature, and in combination with melphalan induces a long-lasting T-cell therapeutic response and immune memory in murine models. Increasing evidence suggests that natural killer (NK) cells act to promote effective T-cell-based antitumor responses. We have analyzed the role of NK cells and dendritic cells (DCs) on two different murine tumor models: WEHI-164 fibrosarcoma and C51 colon carcinoma, in which the combined treatment induces high and low rejection rates respectively...
February 15, 2017: European Journal of Immunology
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