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Journal of Leukocyte Biology

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https://www.readbyqxmd.com/read/27920208/genetic-modification-of-er-hoxb8-osteoclast-precursors-using-crispr-cas9-as-a-novel-way-to-allow-studies-on-osteoclast-biology
#1
Irene Di Ceglie, Guus G H van den Akker, Giuliana Ascone, Bas Ten Harkel, Hans Häcker, Fons A J van de Loo, Marije I Koenders, Peter M van der Kraan, Teun J de Vries, Thomas Vogl, Johannes Roth, Peter L E M van Lent
Osteoclasts are cells specialized in bone resorption. Currently, studies on murine osteoclasts are primarily performed on bone marrow-derived cells with the use of many animals and limited cells available. ER-Hoxb8 cells are conditionally immortalized monocyte/macrophage murine progenitor cells, recently described to be able to differentiate toward functional osteoclasts. Here, we produced an ER-Hoxb8 clonal cell line from C57BL/6 bone marrow cells that strongly resembles phenotype and function of the conventional bone marrow-derived osteoclasts...
December 5, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27899415/role-of-chemokine-receptors-and-intestinal-epithelial-cells-in-the-mucosal-inflammation-and-tolerance
#2
REVIEW
Neeraja Kulkarni, Manisha Pathak, Girdhari Lal
The intestinal epithelial lining is a very dynamic interface, where multiple interactions occur with the external world. The intestinal epithelial barrier is continuously exposed to a huge load of commensal microorganisms, food-borne antigens, as well as invading enteropathogens. Intestinal epithelial cells (IECs) and underlying immune cells are the main players in maintaining the delicate balance between gut tolerance and inflammation. IECs deferentially express the variety of chemokines and chemokine receptors, and these receptor-ligand interactions not only mediate the infiltration and activation of immune cells but also switch on the survival cascades in IECs...
November 29, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27895165/rats-with-a-missense-mutation-in-atm-display-neuroinflammation-and-neurodegeneration-subsequent-to-accumulation-of-cytosolic-dna-following-unrepaired-dna-damage
#3
Hazel Quek, John Luff, KaGeen Cheung, Sergei Kozlov, Magtouf Gatei, C Soon Lee, Mark C Bellingham, Peter G Noakes, Yi Chieh Lim, Nigel L Barnett, Steven Dingwall, Ernst Wolvetang, Tomoji Mashimo, Tara L Roberts, Martin F Lavin
Mutations in the ataxia-telangiectasia (A-T)-mutated (ATM) gene give rise to the human genetic disorder A-T, characterized by immunodeficiency, cancer predisposition, and neurodegeneration. Whereas a series of animal models recapitulate much of the A-T phenotype, they fail to present with ataxia or neurodegeneration. We describe here the generation of an Atm missense mutant [amino acid change of leucine (L) to proline (P) at position 2262 (L2262P)] rat by intracytoplasmic injection (ICSI) of mutant sperm into oocytes...
November 28, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27895164/mysm1-dependent-checkpoints-in-b-cell-lineage-differentiation-and-b-cell-mediated-immune-response
#4
Michael Förster, Kyo Farrington, Jessica C Petrov, Jad I Belle, Barbara C Mindt, Mariko Witalis, Claudia U Duerr, Jörg H Fritz, Anastasia Nijnik
MYSM1 is a chromatin-binding histone deubiquitinase. MYSM1 mutations in humans result in lymphopenia whereas loss of Mysm1 in mice causes severe hematopoietic abnormalities, including an early arrest in B cell development. However, it remains unknown whether MYSM1 is required at later checkpoints in B cell development or for B cell-mediated immune responses. We analyzed conditional mouse models Mysm1(fl/fl)Tg.mb1-cre, Mysm1(fl/fl)Tg.CD19-cre, and Mysm1(fl/fl)Tg.CD21-cre with inactivation of Mysm1 at prepro-B, pre-B, and follicular B cell stages of development...
November 28, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27881605/monocytes-and-dendritic-cells-are-the-primary-sources-of-interleukin-37-in-human-immune-cells
#5
Ina Rudloff, Steven X Cho, Jason C Lao, Devi Ngo, Matthew McKenzie, Claudia A Nold-Petry, Marcel F Nold
The interleukin (IL)-1 family member IL-37 is one of few anti-inflammatory cytokines, and it is capable of countering a broad spectrum of proinflammatory assaults. Although it is known that leukocytes are a major source of IL-37, knowledge on IL-37 production and secretion in specific immune cell types remains limited. Thus, we investigated IL-37 mRNA expression as well as protein production and secretion in human PBMCs. In PBMCs stimulated with agonists of Toll-like receptors (TLRs) 1-6 and 9, IL1F7 (the IL-37-encoding gene) was induced up to 9-fold, peaked at 6-8 h and returned to steady-state at 72 h...
November 23, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27881604/cd11d-%C3%AE-2-integrin-expression-on-human-nk-b-and-%C3%AE-%C3%AE-t-cells
#6
Gabrielle M Siegers, Christy R Barreira, Lynne-Marie Postovit, Gregory A Dekaban
The CD11d integrin is expressed on the cell surface of leukocytes that belong to the myeloid lineage, but its expression on lymphocytes remains unexplored. To test the hypothesis that CD11d is expressed on lymphocyte subsets, we employed a multicolor flow cytometry panel to identify CD11d expression on B, NK, CD4(+) and CD8(+) αβ T cells (αβTc), and γδ T cells (γδTc) in human PBMC samples. CD11d was highly expressed on NK cells, B cells, and γδTc, but not αβTc. CD11d expression was higher on freshly isolated γδTc compared with αβTc from healthy donors, yet both inter- and intradonor variability was evident...
November 23, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27881603/a-protective-role-of-il-37-in-cancer-a-new-hope-for-cancer-patients
#7
REVIEW
Ayoub Abulkhir, Suzanne Samarani, Devendra Amre, Michel Duval, Elie Haddad, Daniel Sinnett, Jean-Marie Leclerc, Caroline Diorio, Ali Ahmad
IL-37 is a cytokine belonging to the IL-1 family. Although discovered in silico in 2000, significant advances in the understanding of its biology were made only in recent years. It is a member of the family with potent anti-inflammatory and immunosuppressive properties. It is produced as a precursor without a classic signal peptide. The precursor is cleaved into mature form in the cytoplasm by caspase-1. A small fraction of the cleaved IL-37 binds SMAD-3, translocates to the nucleus, and suppresses transcription of several proinflammatory genes...
November 23, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27837018/role-of-dendritic-cell-maturation-factors-produced-by-human-invariant-nkt-cells-in-immune-tolerance
#8
Hyeong-Woo Lee, Hyun Bae Jie, Paul L Bollyky, David Sarracino, Tong-Soo Kim, Brian S Wilson
In this study, we used the culture supernatant of iNKT cells to identify human myeloid DC maturation factors produced by human CD4(+) iNKT cells. S100A8 had a strong maturation effect. Notably, the recombinant S100A8 protein displayed properties of DC maturation functioning, and the induction of DC differentiation by both the purified and the recombinant protein were blocked by anti-S100A8 and anti-TLR-4 mAbs. DC differentiation induced by anti-major histocompatibility complex class II/CD1d Ab, S100A8, or both was qualitatively indistinguishable from that induced by the coculture of DCs and iNKT cells or via culture supplementation with supernatants from activated CD4(+) iNKT cells...
November 11, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27837017/differing-rates-of-antibody-acquisition-to-merozoite-antigens-in-malaria-implications-for-immunity-and-surveillance
#9
Fiona J McCallum, Kristina M Persson, Freya J I Fowkes, Linda Reiling, Cleopatra K Mugyenyi, Jack S Richards, Julie A Simpson, Thomas N Williams, Paul R Gilson, Anthony N Hodder, Paul R Sanders, Robin F Anders, David L Narum, Chetan Chitnis, Brendan S Crabb, Kevin Marsh, James G Beeson
Antibodies play a key role in acquired human immunity to Plasmodium falciparum (Pf) malaria and target merozoites to reduce or prevent blood-stage replication and the development of disease. Merozoites present a complex array of antigens to the immune system, and currently, there is only a partial understanding of the targets of protective antibodies and how responses to different antigens are acquired and boosted. We hypothesized that there would be differences in the rate of acquisition of antibodies to different antigens and how well they are boosted by infection, which impacts the acquisition of immunity...
November 11, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27837016/chronic-alcohol-consumption-inhibits-peripheral-nk-cell-development-and-maturation-by-decreasing-the-availability-of-il-15
#10
Faya Zhang, Alex Little, Hui Zhang
NK cells are innate immune cells and have important roles in antiviral and antitumor immunity. Based on the transcriptional regulation, organ distribution, and cell function, NK cells have recently been further divided into cytotoxic conventional NK cells (cNK) and noncytotoxic helper-like group 1 innate lymphoid cells (ILC1s). It is well known that chronic alcohol consumption decreases peripheral NK cell number and cytolytic activity; however, the underlying mechanism remains to be elucidated. How chronic alcohol consumption affects ILC1s is, to our knowledge, completely unexplored...
November 11, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27821468/transient-reduction-in-iga-and-igg-memory-b-cell-numbers-in-young-ebv-seropositive-children-the-generation-r-study
#11
Diana van den Heuvel, Michelle A E Jansen, Andrew I Bell, Alan B Rickinson, Vincent W V Jaddoe, Jacques J M van Dongen, Henriette A Moll, Menno C van Zelm
The EBV is known to persist in memory B cells, but it remains unclear how this affects cell numbers and humoral immunity. We here studied EBV persistence in memory B cell subsets and consequences on B cell memory in young children. EBV genome loads were quantified in 6 memory B cell subsets in EBV(+) adults. The effects of EBV infection on memory B cell numbers and vaccination responses were studied longitudinally in children within the Generation R population cohort between 14 mo and 6 yr of age. EBV genomes were more numerous in CD27(+)IgG(+), CD27(+)IgA(+), and CD27(-)IgA(+) memory B cells than in IgM-only, natural effector, and CD27(-)IgG(+) B cells...
November 7, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27810946/bacterial-secretion-systems-and-regulation-of-inflammasome-activation
#12
REVIEW
Dmitry Ratner, M Pontus A Orning, Egil Lien
Innate immunity is critical for host defenses against pathogens, but many bacteria display complex ways of interacting with innate immune signaling, as they may both activate and evade certain pathways. Gram-negative bacteria can exhibit specialized nanomachine secretion systems for delivery of effector proteins into mammalian cells. Bacterial types III, IV, and VI secretion systems (T3SS, T4SS, and T6SS) are known for their impact on caspase-1-activating inflammasomes, necessary for producing bioactive inflammatory cytokines IL-1β and IL-18, key participants of anti-bacterial responses...
November 3, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27810945/pregnancy-promotes-tolerance-to-future-offspring-by-programming-selective-dysfunction-in-long-lived-maternal-t-cells
#13
Brendan M Barton, Rong Xu, E John Wherry, Paige M Porrett
Fetal antigen available during pregnancy induces the proliferation of maternal T cells. It is unknown, however, whether these antigen-activated T cells differentiate into long-lived memory T cells that are capable of mediating rapid-recall responses to tissue antigens. To test the hypothesis that pregnancy induces an alternative fate in fetal-specific maternal T cells, we used a murine model to track longitudinally fetal-specific T cells in pregnant and postpartum animals and test the response of these cells when challenged with the same antigen during sequential pregnancy or skin transplantation...
November 3, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27810944/pattern-recognition-receptor-immunomodulation-of-innate-immunity-as-a-strategy-to-limit-the-impact-of-influenza-virus
#14
REVIEW
Angela Pizzolla, Jeffery M Smith, Andrew G Brooks, Patrick C Reading
Influenza remains a major global health issue and the effectiveness of current vaccines and antiviral drugs is limited by the continual evolution of influenza viruses. Therefore, identifying novel prophylactic or therapeutic treatments that induce appropriate innate immune responses to protect against influenza infection would represent an important advance in efforts to limit the impact of influenza. Cellular pattern recognition receptors (PRRs) recognize conserved structures expressed by pathogens to trigger intracellular signaling cascades, promoting expression of proinflammatory molecules and innate immunity...
November 3, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27803128/stat-mutations-as-program-switchers-turning-primary-immunodeficiencies-into-autoimmune-diseases
#15
REVIEW
Tiziana Lorenzini, Laura Dotta, Mauro Giacomelli, Donatella Vairo, Raffaele Badolato
STAT proteins are a family of transcription factors that mediate cellular response to cytokines and growth factors. Study of patients with familial susceptibility to pathogens and/or autoimmune diseases has led to the identification of 7 inherited disorders that are caused by mutations of 4 STAT family genes. Homozygous or compound heterozygous mutations of STAT1 lead to complete or partial forms of STAT1 deficiency that are associated with susceptibility to intracellular pathogens and herpetic infections. Patients with heterozygous STAT1 gain-of-function (GOF) mutations usually present with chronic mucocutaneous candidiasis (CMC) but may also experience bacterial and viral infections, autoimmune manifestations, lymphopenia, cerebral aneurysms, and increased risk to develop tumors...
November 1, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27803127/phospholipases-at-the-crossroads-of-the-immune-system-and-the-pathogenesis-of-hiv-1-infection
#16
REVIEW
Serena Cecchetti, Francesca Spadaro, Sandra Gessani, Franca Podo, Laura Fantuzzi
Multiple host factors and their interactions with viral proteins contribute to the complexity of HIV-1 pathogenesis and disease progression. The virus exploits the cell-signaling networks to prepare the ground for viral replication, to affect functions of either infected or uninfected bystander cells, and to evade the immune response. These events are hallmarks of HIV-1 pathogenesis that lead toward AIDS. Phospholipases are essential mediators of intracellular and intercellular signaling. They function as phospholipid-hydrolyzing enzymes, generating many bioactive lipid mediators or second messengers, which control multiple cellular functions, thus regulating a variety of physiologic and pathophysiologic processes...
November 1, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27793959/interleukin-32-a-novel-player-in-the-control-of-infectious-diseases
#17
REVIEW
Fátima Ribeiro-Dias, Rodrigo Saar Gomes, Lucas Luiz de Lima Silva, Jéssica Cristina Dos Santos, Leo A B Joosten
Interleukin 32 (IL-32) is a proinflammatory cytokine, expressed as 9 distinct isoforms. The most active isoform is the predominantly intracellular-functioning IL-32γ. Involvement of IL-32 in infectious diseases is increasingly being appreciated. Production of IL-32 promotes pathways that serve to control bacterial infection, especially those caused by mycobacteria. A similar role for this cytokine is observed in the cellular response to viral infections. In addition to its protective effects against microorganisms, IL-32 is involved in immunopathogenesis of some infectious diseases...
October 28, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27780875/molecular-mechanisms-of-innate-memory-and-tolerance-to-lps
#18
REVIEW
John J Seeley, Sankar Ghosh
LPS is a potent trigger of macrophage-mediated inflammation. However, prolonged exposure to LPS induces a state of tolerance that reprograms the inflammatory response, resulting in reduced inflammatory cytokine production in vitro and in vivo. Recent evidence suggests that LPS tolerance also increases the expression of a subset of genes that may protect animals from systemic infection while they are in the tolerized state. However, a molecular basis for these selective changes in inflammatory gene expression during LPS tolerance has remained elusive...
October 25, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27765819/brucella-abortus-down-regulates-mhc-class-ii-by-the-il-6-dependent-inhibition-of-ciita-through-the-downmodulation-of-ifn-regulatory-factor-1-irf-1
#19
Lis N Velásquez, M Ayelén Milillo, M Victoria Delpino, Aldana Trotta, Pablo Fernández, Roberto G Pozner, Roland Lang, Luciana Balboa, Guillermo H Giambartolomei, Paula Barrionuevo
Brucella abortus is an intracellular pathogen capable of surviving inside of macrophages. The success of B. abortus as a chronic pathogen relies on its ability to orchestrate different strategies to evade the adaptive CD4(+) T cell responses that it elicits. Previously, we demonstrated that B. abortus inhibits the IFN-γ-induced surface expression of MHC class II (MHC-II) molecules on human monocytes, and this phenomenon correlated with a reduction in antigen presentation. However, the molecular mechanisms, whereby B...
October 20, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27733582/synovial-il-21-tnf-producing-cd4-t-cells-induce-joint-destruction-in-rheumatoid-arthritis-by-inducing-matrix-metalloproteinase-production-by-fibroblast-like-synoviocytes
#20
Maria C Lebre, Pedro L Vieira, Man Wai Tang, Saïda Aarrass, Boy Helder, Thomas Newsom-Davis, Paul P Tak, Gavin R Screaton
Bone and cartilage destruction is one of the key manifestations of rheumatoid arthritis (RA). Although the role of T helper (Th)17 cells in these processes is clear, the role of IL-21-producing cells T cells has been neglected. We sought to investigate the role of IL-21 in RA by focusing on the functional characteristics of the main producers of this cytokine, synovial CD4(+)IL-21(+) T cells. We show that the frequency of both synovial fluid (SF) CD4(+)IL-21(+) or CD4(+)IL-21(+)TNF(+) T cells in patients with RA was significantly higher compared with patients with psoriatic arthritis (PsA)...
October 12, 2016: Journal of Leukocyte Biology
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