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European Journal of Immunology

Anne Dommaschk, Lara F Lang, Regina Maus, Jennifer Stolper, Tobias Welte, Ulrich A Maus
Nasopharyngeal colonization with Streptococcus pneumoniae (the pneumococcus) is known to mount protective adaptive immune responses in rodents and humans. However, the cellular response of the nasopharyngeal compartment to pneumococcal colonization and its importance for the ensuing adaptive immune response is only partially defined. Here we show that nasopharyngeal colonization with S. pneumoniae triggered substantial expansion of both integrin αE (CD103) positive dendritic cells (DC) and T lymphocytes in nasopharynx, nasal-associated lymphoid tissue (NALT) and cervical lymph nodes (CLN) of WT mice...
March 15, 2018: European Journal of Immunology
David Schub, Mathias Fousse, Julia Elsäßer, Klaus Faßbender, Urban Sester, Tina Schmidt, Martina Sester
No abstract text is available yet for this article.
March 14, 2018: European Journal of Immunology
Livius Penter, Kerstin Dietze, Lars Bullinger, Jörg Westermann, Hans-Peter Rahn, Leo Hansmann
No abstract text is available yet for this article.
March 14, 2018: European Journal of Immunology
Yohei Mikami, Gianluca Scarno, Beatrice Zitti, Han-Yu Shih, Yuka Kanno, Angela Santoni, John J O'Shea, Giuseppe Sciumè
Innate lymphoid cells (ILCs) producing IL-22 and/or IL-17, designated as ILC3, comprise a heterogeneous subset of cells involved in regulation of gut barrier homeostasis and inflammation. Exogenous environmental cues in conjunction with regulated expression of endogenous factors are key determinants of plasticity of ILC3 towards the type 1 fate. Herein, by using mouse models and transcriptomic approaches, we defined at the molecular level, initial events driving ILC3 expressing natural cytotoxicity receptors (NCR+ ILC3) to acquire type 1 features...
March 9, 2018: European Journal of Immunology
Yasuyuki Negishi, Tomoko Ichikawa, Toshiyuki Takeshita, Hidemi Takahashi
Unexpected fetal loss is one of the common complications of pregnancy; however, the pathogenesis of many miscarriages, particularly those not associated with infections, is unknown. We previously found that activated DEC-205+ dendritic cells (DCs) and NK1.1+ invariant natural killer T (iNKT) cells are recruited into the myometrium of mice when miscarriage is induced by the intraperitoneal administration of α-galactosylceramide (α-GalCer). Here we demonstrate that the adoptive transfer of DEC-205+ bone marrow-derived DCs cocultured with α-GalCer (DEC-205+ BMDCs-c/w-α-GalCer) directly induced marked fetal loss by syngeneic pregnant C57BL/6 (B6) mice and allogeneic mice (B6 (♀) × BALB/c (♂)), which was accompanied by the accumulation of activated iNKT cells in the myometrium...
March 9, 2018: European Journal of Immunology
Katy A Lloyd, Johanna Steen, Khaled Amara, Philip J Titcombe, Lena Israelsson, Susanna L Lundström, Diana Zhou, Roman A Zubarev, Evan Reed, Luca Piccoli, Cem Gabay, Antonio Lanzavecchia, Dominique Baeten, Karin Lundberg, Daniel L Mueller, Lars Klareskog, Vivianne Malmström, Caroline Grönwall
Autoreactive B cells have a central role in the pathogenesis of rheumatoid arthritis (RA), and recent findings have proposed that anti-citrullinated protein autoantibodies (ACPA) may be directly pathogenic. Herein, we demonstrate the frequency of variable-region glycosylation in single-cell cloned mAbs. A total of 14 ACPA mAbs were evaluated for predicted N-linked glycosylation motifs in silico, and compared to 452 highly-mutated mAbs from RA patients and controls. Variable region N-linked motifs (N-X-S/T) were strikingly prevalent within ACPA (100%) compared to somatically hypermutated (SHM) RA bone marrow plasma cells (21%), and synovial plasma cells from seropositive (39%) and seronegative RA (7%)...
March 7, 2018: European Journal of Immunology
Chi Ching Goh, Maximilien Evrard, Shu Zhen Chong, Yingrou Tan, Leonard De Li Tan, Karen Wei Weng Teng, Wolfgang Weninger, David Laurence Becker, Hong Liang Tey, Evan William Newell, Bin Liu, Lai Guan Ng
Pressure ulcers are a chronic problem for patients or the elderly who require extended periods of bed rest. The formation of ulcers is due to repeated cycles of ischemia-reperfusion (IR), which initiates an inflammatory response. Advanced ulcers disrupt the skin barrier, resulting in further complications. To date, the immunological aspect of skin IR has been understudied, partly due to the complexity of the skin immune cells. Through a combination of mass cytometry, confocal imaging and intravital multiphoton imaging, this study establishes a workflow for multidimensionality single cell analysis of skin myeloid responses in the context of IR injury with high spatiotemporal resolution...
March 6, 2018: European Journal of Immunology
Yayun Chen, Fan Meng, Bingyu Wang, Liangmei He, Yangbin Liu, Zhiping Liu
An atypical guanine exchange factor, Dock2 is specifically expressed in hematopoietic cells and regulates activation and migration of immune cells through activating Ras-related C3 botulinum toxin substrate (Rac). Dock2 was shown to be critical in the development of various inflammatory diseases, including allergic diseases, HIV infection, and graft rejection in organ transplantation. DOCK2 mutation in infants was recently identified to be associated with T and B cell combined immunodeficiency. Furthermore, Dock2 is involved in host protection during enteric bacterial infection and is also associated with the proliferation of cancer cells...
March 6, 2018: European Journal of Immunology
Hristo Georgiev, Inga Ravens, Georgia Papadogianni, Bernard Malissen, Reinhold Förster, Günter Bernhardt
No abstract text is available yet for this article.
March 5, 2018: European Journal of Immunology
Georg Petkau, Yohei Kawano, Ingrid Wolf, Marko Knoll, Fritz Melchers
Hematopoietic stem cells and lineage-uncommitted progenitors are able to home to the bone marrow upon transplantation and reconstitute the host with hematopoietic progeny. Expression of miR221 in B-lineage committed preBI-cells induces their capacity to home to the bone marrow. However, the molecular mechanisms underlying miR221-controlled bone marrow homing and retention remain poorly understood. Here, we demonstrate, that miR221 regulates bone marrow retention of such B-cell precursors by targeting PTEN, thus enhancing PI3K signaling in response to the chemokine CXCL12...
March 5, 2018: European Journal of Immunology
Ilija Brizić, Božo Sušak, Maja Arapović, Peter C Huszthy, Lea Hiršl, Daria Kveštak, Vanda Juranić Lisnić, Mijo Golemac, Ester Pernjak Pugel, Jelena Tomac, Annette Oxenius, William J Britt, Jurica Arapović, Astrid Krmpotić, Stipan Jonjić
Congenital HCMV infection is a leading infectious cause of long-term neurodevelopmental sequelae. Infection of newborn mice with MCMV intraperitoneally is a well-established model of congenital HCMV infection, which best recapitulates the hematogenous route of virus spread to brain and subsequent pathology. Here we used this model to investigate the role, dynamics and phenotype of CD8+ T cells in the brain following infection of newborn mice. We show that CD8+ T cells infiltrate the brain and form a pool of tissue-resident memory T cells (TRM cells) that persist for lifetime...
March 3, 2018: European Journal of Immunology
Zhen Bian, Ahmed Mansour Abdelaal, Lei Shi, Hongwei Liang, Lanqiao Xiong, Koby Kidder, Mahathi Venkataramani, Courtney Culpepper, Ke Zen, Yuan Liu
Although previous reports suggest that tumor-induced myeloid-derived suppressor cells (MDSC) inhibit T cells by L-arginine depletion through arginase-1 activity, we herein show that arginase-1 is neither inherently expressed in MDSC nor required for MDSC-mediated inhibition. Employing Percoll density gradients, large expansions of MDSC in the bone marrow of tumor-bearing mice were isolated and demonstrated potent inhibition in T cell proliferation activated by TCR-ligation, Concanavalin A, PMA plus ionomycin, or IL-2...
February 28, 2018: European Journal of Immunology
Nico Andreas, Marc Riemann, Carla N Castro, Marco Groth, Ievgen Koliesnik, Christian Engelmann, Tim Sparwasser, Thomas Kamradt, Ronny Haenold, Falk Weih
The NF-κB transcription factor subunit RelB is important for the full activation of conventional dendritic cells (cDCs) during T-cell-dependent immune responses. Although the number of splenic DCs is greatly reduced in RelBnull mice, the cause and consequences of this deficiency are currently unknown. To circumvent the impact of the pleiotropic defects in RelBnull mice we used a reporter model for RelB expression (RelBKatushka mice) and conditionally deleted RelB in DCs (RelBCD11c-Cre mice). Thereby, we can show here that RelB is essential for the differentiation of a CD117+ CD172a+ cDC subpopulation which highly expresses RelB...
February 27, 2018: European Journal of Immunology
Tao Zhang, Juhua Zhou, Gene Chi Wai Man, Kam Tong Leung, Bo Liang, Bo Xiao, Xinting Ma, Shaoyan Huang, Huaxiang Huang, Venkatesh L Hegde, Yin Zhong, Yanmin Li, Grace Wing Shan Kong, Alice KaWah Yiu, Joseph Kwong, Pak Cheung Ng, Prakash S Nagarkatti, Mitzi Nagarkatti, Chi Chiu Wang
Endometriosis affects women of reproductive age via unclear immunological mechanism(s). Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of myeloid cells with potent immunosuppressive and angiogenic properties. Here we found MDSCs significantly increased in the peripheral blood of patients with endometriosis and in the peritoneal cavity of a mouse model of surgically-induced endometriosis. Majority of MDSCs were granulocytic, produced ROS and arginase, and suppressed T cell proliferation. Depletion of MDSCs by antiGr-1 antibody dramatically suppressed development of endometrial lesions in mice...
February 20, 2018: European Journal of Immunology
Eric Haertel, Natasha Joshi, Paul Hiebert, Manfred Kopf, Sabine Werner
Healing of skin wounds is orchestrated by various types of immune cells, but little is known about the role of FoxP3+ regulatory T cells (Tregs) in this process. Here we determined if Tregs are important for wound healing in normal mice and if they contribute to the accelerated healing of mice overexpressing the growth and differentiation factor activin. Diphtheria-toxin induced Treg depletion prior to injury caused impaired healing characterized by delayed re-epithelialization, reduced wound contraction and impaired vessel maturation...
February 19, 2018: European Journal of Immunology
Judith-Mira Pohl, Julia K Volke, Stephanie Thiebes, Alexandra Brenzel, Kerstin Fuchs, Nicolas Beziere, Walter Ehrlichmann, Bernd J Pichler, Anthony Squire, Faikah Gueler, Daniel R Engel
The hemolytic uremic syndrome (HUS) is a life-threatening disease of the kidney that is induced by Shiga toxin-producing E.coli. Major changes in the monocytic compartment and in CCR2-binding chemokines have been observed. However, the specific contribution of CCR2-dependent Gr1high monocytes is unknown. To investigate the impact of these monocytes during HUS, we injected a combination of LPS and Shiga toxin into mice. We observed an impaired kidney function and elevated levels of the CCR2-binding chemokine CCL2 after Shiga toxin/LPS- injection, thus suggesting Gr1high monocyte infiltration into the kidney...
February 14, 2018: European Journal of Immunology
Konrad Haberland, Jochen A Ackermann, Natacha Ipseiz, Stephan Culemann, Katharina Pracht, Matthias Englbrecht, Hans-Martin Jäck, Georg Schett, Wolfgang Schuh, Gerhard Krönke
Eosinophils were reported to serve as an essential component of the plasma cell niche within the bone marrow. As the potential contribution of eosinophils to humoral immunity has remained incompletely understood, we aimed to further characterize their role during antibody responses and to additionally investigate their role in autoimmune disease. Contrary to our expectations and the currently prevailing paradigm, we found that eosinophils are fully dispensable for the survival of murine bone marrow plasma cells and accordingly do not contribute to antibody production and autoantibody-mediated disease...
February 14, 2018: European Journal of Immunology
Alexandra Bortnick, Irene Chernova, Sean P Spencer, David Allman
Lasting antibody responses are maintained by long-lived plasma cells, which are thought to lodge in the bone marrow (BM) in specialized survival niches. Eosinophils have been reported to function as a critical component of the BM survival niche where they are thought to provide pro-survival signals to nearby plasma cells. Recent work shows that many BM plasma cells are recently generated and chiefly short-lived cells, raising the possibility that rare plasma cell-eosinophil interactions are a rate-limiting step needed to establish lasting humoral immunity...
February 14, 2018: European Journal of Immunology
Shashirekha Mundhra, Ruslana Bryk, Natalie Hawryluk, Tuo Zhang, Xiuju Jiang, Carl F Nathan
Genetic deficiency of protein kinase R (PKR) in mice was reported to enhance macrophage activation in vitro in response to interferon-γ (IFNγ) and to reduce the burden of Mycobacterium tuberculosis (Mtb) in vivo (Wu et al. PloS One. 2012 7:e30512). Consistent with this, treatment of wild-type (WT) macrophages in vitro with a novel PKR inhibitor (Bryk et al., Bioorg. Med. Chem. Lett. 2011 21:4108-4114) also enhanced IFN-γ-dependent macrophage activation (Wu et al. PloS One. 2012 7:e30512). Here we show that co-treatment with IFN-γ and a new PKR inhibitor identified herein to be highly but not completely selective likewise induced macrophages to produce more reactive nitrogen intermediates (RNI) and tumor necrosis factor alpha (TNF-α) and less interleukin 10 (IL-10) than seen with IFN-γ alone...
February 13, 2018: European Journal of Immunology
Alexander Leithner, Joerg Renkawitz, Ingrid De Vries, Robert Hauschild, Hans Häcker, Michael Sixt
Dendritic cells (DCs) are sentinels of the adaptive immune system that reside in peripheral organs of mammals. Upon pathogen encounter, they undergo maturation and up-regulate the chemokine receptor CCR7 that guides them along gradients of its chemokine ligands CCL19 and 21 to the next draining lymph node. There, DCs present peripherally acquired antigen to naïve T cells, thereby triggering adaptive immunity. This article is protected by copyright. All rights reserved.
February 13, 2018: European Journal of Immunology
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