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Journal of Immunology: Official Journal of the American Association of Immunologists

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https://www.readbyqxmd.com/read/28341672/activation-of-myeloid-tlr4-mediates-t-lymphocyte-polarization-after-traumatic-brain-injury
#1
Molly Braun, Kumar Vaibhav, Nancy Saad, Sumbul Fatima, Darrell W Brann, John R Vender, Lei P Wang, Md Nasrul Hoda, Babak Baban, Krishnan M Dhandapani
Traumatic brain injury (TBI) is a major public health issue, producing significant patient mortality and poor long-term outcomes. Increasing evidence suggests an important, yet poorly defined, role for the immune system in the development of secondary neurologic injury over the days and weeks following a TBI. In this study, we tested the hypothesis that peripheral macrophage infiltration initiates long-lasting adaptive immune responses after TBI. Using a murine controlled cortical impact model, we used adoptive transfer, transgenic, and bone marrow chimera approaches to show increased infiltration and proinflammatory (classically activated [M1]) polarization of macrophages for up to 3 wk post-TBI...
March 24, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28341671/lipopolysaccharide-elicited-tslpr-expression-enriches-a-functionally-discrete-subset-of-human-cd14-cd1c-monocytes
#2
Francesco Borriello, Raffaella Iannone, Sarah Di Somma, Viviana Vastolo, Giuseppe Petrosino, Feliciano Visconte, Maddalena Raia, Giulia Scalia, Stefania Loffredo, Gilda Varricchi, Maria Rosaria Galdiero, Francescopaolo Granata, Luigi Del Vecchio, Giuseppe Portella, Gianni Marone
Thymic stromal lymphopoietin (TSLP) is a cytokine produced mainly by epithelial cells in response to inflammatory or microbial stimuli and binds to the TSLP receptor (TSLPR) complex, a heterodimer composed of TSLPR and IL-7 receptor α (CD127). TSLP activates multiple immune cell subsets expressing the TSLPR complex and plays a role in several models of disease. Although human monocytes express TSLPR and CD127 mRNAs in response to the TLR4 agonist LPS, their responsiveness to TSLP is poorly defined. We demonstrate that TSLP enhances human CD14(+) monocyte CCL17 production in response to LPS and IL-4...
March 24, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28341670/prime-boost-immunization-eliminates-metastatic-colorectal-cancer-by-producing-high-avidity-effector-cd8-t-cells
#3
Bo Xiang, Trevor R Baybutt, Lisa Berman-Booty, Michael S Magee, Scott A Waldman, Vitali Y Alexeev, Adam E Snook
Heterologous prime-boost immunization with plasmid DNA and viral vector vaccines is an emerging approach to elicit CD8(+) T cell-mediated immunity targeting pathogens and tumor Ags that is superior to either monotherapy. Yet, the mechanisms underlying the synergy of prime-boost strategies remain incompletely defined. In this study, we examine a DNA and adenovirus (Ad5) combination regimen targeting guanylyl cyclase C (GUCY2C), a receptor expressed by intestinal mucosa and universally expressed by metastatic colorectal cancer...
March 24, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28330901/azacitidine-mitigates-graft-versus-host-disease-via-differential-effects-on-the-proliferation-of-t-effectors-and-natural-regulatory-t-cells-in-vivo
#4
Matthew L Cooper, Jaebok Choi, Darja Karpova, Kiran Vij, Julie Ritchey, Mark A Schroeder, John F DiPersio
Azacitidine (AzaC) mitigates graft-versus-host disease (GvHD) in both murine preclinical transplant models and in human clinical trials while maintaining a robust graft-versus-leukemia effect. Previous studies have failed to investigate the role of natural regulatory T cells (nTregs) on the mitigation of GvHD by AzaC, instead focusing on the generation of suppressive Tregs (CD4(+)CD25(+)FOXP3(+)) through the in vivo conversion of alloreactive donor T effectors (Teffs; CD4(+)CD25(-)FOXP3(-)) and the direct antiproliferative effects of AzaC on allogeneic T cells...
March 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28330900/adaptive-immune-responses-to-zika-virus-are-important-for-controlling-virus-infection-and-preventing-infection-in-brain-and-testes
#5
Clayton W Winkler, Lara M Myers, Tyson A Woods, Ronald J Messer, Aaron B Carmody, Kristin L McNally, Dana P Scott, Kim J Hasenkrug, Sonja M Best, Karin E Peterson
The recent association between Zika virus (ZIKV) and neurologic complications, including Guillain-Barré syndrome in adults and CNS abnormalities in fetuses, highlights the importance in understanding the immunological mechanisms controlling this emerging infection. Studies have indicated that ZIKV evades the human type I IFN response, suggesting a role for the adaptive immune response in resolving infection. However, the inability of ZIKV to antagonize the mouse IFN response renders the virus highly susceptible to circulating IFN in murine models...
March 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28330899/il-24-promotes-pseudomonas-aeruginosa-keratitis-in-c57bl-6-mouse-corneas
#6
Bing X Ross, Nan Gao, Xinhan Cui, Theodore J Standiford, Jianjiang Xu, Fu-Shin X Yu
The aim of this study was to elucidate the expression and functions of IL-24 in C57BL/6 mouse corneas in response to Pseudomonas aeruginosa infection. Among IL-20R cytokines, only IL-24 was induced at both mRNA and protein levels by infection at early time points. The upregulation of IL-24 was dampened by flagellin pretreatment, which protects the corneas from microbial infection. Time course studies revealed bimodal early and later peaks of IL-24 expression, a pattern shared with suppressor of cytokine signaling (SOCS)3 but not IL-1β or IL-6...
March 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28330898/antigen-presenting-human-%C3%AE-%C3%AE-t-cells-promote-intestinal-cd4-t-cell-expression-of-il-22-and-mucosal-release-of-calprotectin
#7
Christopher J Tyler, Neil E McCarthy, James O Lindsay, Andrew J Stagg, Bernhard Moser, Matthias Eberl
The cytokine IL-22 plays a critical role in mucosal barrier defense, but the mechanisms that promote IL-22 expression in the human intestine remain poorly understood. As human microbe-responsive Vγ9/Vδ2 T cells are abundant in the gut and recognize microbiota-associated metabolites, we assessed their potential to induce IL-22 expression by intestinal CD4(+) T cells. Vγ9/Vδ2 T cells with characteristics of APCs were generated from human blood and intestinal organ cultures, then cocultured with naive and memory CD4(+) T cells obtained from human blood or the colon...
March 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28330897/rip2-is-required-for-nod2-mediated-lysozyme-sorting-in-paneth-cells
#8
Haifang Wang, Xinwen Zhang, Zhanguang Zuo, Qin Zhang, Ying Pan, Benhua Zeng, Wenxia Li, Hong Wei, Zhihua Liu
Paneth cells play an important role in maintaining intestinal homeostasis by secreting a large number of antimicrobial peptides into the intestinal lumen. In this study, we found that Rip2 is required for lysozyme sorting in Paneth cells in a manner that is dependent on Nod2, LRRK2, and Rab2a. Rip2 deficiency in mouse led to lysosomal degradation of lysozyme in Paneth cells and prevented the recruitment of Rab2a onto dense core vesicles (DCVs). Like Nod2 and LRRK2, Rip2 localizes to DCVs in Paneth cells, and its DCV localization depends on Nod2 and LRRK2...
March 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28330896/cell-specific-variation-in-e-selectin-ligand-expression-among-human-peripheral-blood-mononuclear-cells-implications-for-immunosurveillance-and-pathobiology
#9
Mariana Silva, Ronald Kam Fai Fung, Conor Brian Donnelly, Paula Alexandra Videira, Robert Sackstein
Both host defense and immunopathology are shaped by the ordered recruitment of circulating leukocytes to affected sites, a process initiated by binding of blood-borne cells to E-selectin displayed at target endothelial beds. Accordingly, knowledge of the expression and function of leukocyte E-selectin ligands is key to understanding the tempo and specificity of immunoreactivity. In this study, we performed E-selectin adherence assays under hemodynamic flow conditions coupled with flow cytometry and Western blot analysis to elucidate the function and structural biology of glycoprotein E-selectin ligands expressed on human PBMCs...
March 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28320833/inflammatory-changes-in-bone-marrow-microenvironment-associated-with-declining-b-lymphopoiesis
#10
Domenick E Kennedy, Katherine L Knight
B lymphopoiesis arrests precipitously in rabbits such that by 2-4 mo of age, before sexual maturity, little to no B lymphopoiesis occurs in the bone marrow (BM). Previously, we showed that in mice, adipocytes inhibit B lymphopoiesis in vitro by inducing inflammatory myeloid cells, which produce IL-1β. In this study, we characterized rabbit BM after the arrest of B lymphopoiesis and found a dramatic increase in fat, increased CD11b(+) myeloid cells, and upregulated expression of the inflammatory molecules, IL-1β and S100A9, by the myeloid cells...
March 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28320832/g-csf-receptor-blockade-ameliorates-arthritic-pain-and-disease
#11
Ming-Chin Lee, James A McCubbin, Anne D Christensen, Daniel P Poole, Pradeep Rajasekhar, TinaMarie Lieu, Nigel W Bunnett, Sonia Garcia-Caraballo, Andelain Erickson, Stuart M Brierley, Reem Saleh, Adrian Achuthan, Andrew J Fleetwood, Robin L Anderson, John A Hamilton, Andrew D Cook
G-CSF or CSF-3, originally defined as a regulator of granulocyte lineage development via its cell surface receptor (G-CSFR), can play a role in inflammation, and hence in many pathologies, due to its effects on mature lineage populations. Given this, and because pain is an extremely important arthritis symptom, the efficacy of an anti-G-CSFR mAb for arthritic pain and disease was compared with that of a neutrophil-depleting mAb, anti-Ly6G, in both adaptive and innate immune-mediated murine models. Pain and disease were ameliorated in Ag-induced arthritis, zymosan-induced arthritis, and methylated BSA/IL-1 arthritis by both prophylactic and therapeutic anti-G-CSFR mAb treatment, whereas only prophylactic anti-Ly6G mAb treatment was effective...
March 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28320831/interference-of-the-t-cell-and-antigen-presenting-cell-costimulatory-pathway-using-ctla4-ig-abatacept-prevents-staphylococcal-enterotoxin-b-pathology
#12
Sarah J C Whitfield, Chris Taylor, Jane E Risdall, Gareth D Griffiths, James T A Jones, E Diane Williamson, Sjoerd Rijpkema, Luisa Saraiva, Sandrine Vessillier, A Christopher Green, Alun J Carter
Staphylococcal enterotoxin B (SEB) is a bacterial superantigen that binds the receptors in the APC/T cell synapse and causes increased proliferation of T cells and a cytokine storm syndrome in vivo. Exposure to the toxin can be lethal and cause significant pathology in humans. The lack of effective therapies for SEB exposure remains an area of concern, particularly in scenarios of acute mass casualties. We hypothesized that blockade of the T cell costimulatory signal by the CTLA4-Ig synthetic protein (abatacept) could prevent SEB-dependent pathology...
March 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28314856/ubc9-is-required-for-positive-selection-and-late-stage-maturation-of-thymocytes
#13
Aibo Wang, Xiao Ding, Maud Demarque, Xindong Liu, Deng Pan, Huawei Xin, Bo Zhong, Xiaohu Wang, Anne Dejean, Wei Jin, Chen Dong
SUMOylation is an important posttranslational modification that regulates protein function in diverse biological processes. However, its role in early T cell development has not been genetically studied. UBC9 is the only E2 enzyme for all SUMOylation. In this study, by selectively deleting Ubc9 gene in T cells, we have investigated the functional roles of SUMOylation in T cell development. Loss of Ubc9 results in a significant reduction of CD4 and CD8 single-positive lymphocytes in both thymus and periphery...
March 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28314855/def6-restrains-osteoclastogenesis-and-inflammatory-bone-resorption
#14
Nikolaus Binder, Christine Miller, Masaki Yoshida, Kazuki Inoue, Shinichi Nakano, Xiaoyu Hu, Lionel B Ivashkiv, Georg Schett, Alessandra Pernis, Steven R Goldring, F Patrick Ross, Baohong Zhao
Inflammatory bone resorption mediated by osteoclasts is a major cause of morbidity and disability in many inflammatory disorders, including rheumatoid arthritis (RA). The mechanisms that regulate osteoclastogenesis and bone resorption in inflammatory settings are complex and have not been well elucidated. In this study, we identify the immunoregulator differentially expressed in FDCP 6 homolog (Def6) as a novel inhibitor of osteoclastogenesis in physiological and inflammatory conditions. Def6 deficiency in Def6(-/-) mice enhanced the sensitivity of osteoclast precursors to the physiological osteoclastogenic inducer receptor activator for NF-κB ligand, and Def6(-/-) osteoclasts formed actin rings...
March 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28298526/the-ap-1-transcription-factor-c-jun-promotes-arthritis-by-regulating-cyclooxygenase-2-and-arginase-1-expression-in-macrophages
#15
Nicole Hannemann, Jutta Jordan, Sushmita Paul, Stephen Reid, Hanns-Wolf Baenkler, Sophia Sonnewald, Tobias Bäuerle, Julio Vera, Georg Schett, Aline Bozec
Activation of proinflammatory macrophages is associated with the inflammatory state of rheumatoid arthritis. Their polarization and activation are controlled by transcription factors such as NF-κB and the AP-1 transcription factor member c-Fos. Surprisingly, little is known about the role of the AP-1 transcription factor c-Jun in macrophage activation. In this study, we show that mRNA and protein levels of c-Jun are increased in macrophages following pro- or anti-inflammatory stimulations. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment cluster analyses of microarray data using wild-type and c-Jun-deleted macrophages highlight the central function of c-Jun in macrophages, in particular for immune responses, IL production, and hypoxia pathways...
March 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28298525/the-induction-of-pro-il-1%C3%AE-by-lipopolysaccharide-requires-endogenous-prostaglandin-e2-production
#16
Zbigniew Zasłona, Eva M Pålsson-McDermott, Deepthi Menon, Moritz Haneklaus, Ewelina Flis, Hannah Prendeville, Sarah E Corcoran, Marc Peters-Golden, Luke A J O'Neill
PGE2 has been shown to increase the transcription of pro-IL-1β. However, recently it has been demonstrated that PGE2 can block the maturation of IL-1β by inhibiting the NLRP3 inflammasome in macrophages. These apparently conflicting results have led us to reexamine the effect of PGE2 on IL-1β production. We have found that in murine bone marrow-derived macrophages, PGE2 via the cAMP/protein kinase A pathway is potently inducing IL-1β transcription, as well as boosting the ability of LPS to induce IL-1β mRNA and pro-IL-1β while inhibiting the production of TNF-α...
March 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28298524/novel-noncatalytic-substrate-selective-p38%C3%AE-specific-mapk-inhibitors-with-endothelial-stabilizing-and-anti-inflammatory-activity
#17
Nirav G Shah, Mohan E Tulapurkar, Aparna Ramarathnam, Amanda Brophy, Ramon Martinez, Kellie Hom, Theresa Hodges, Ramin Samadani, Ishwar S Singh, Alexander D MacKerell, Paul Shapiro, Jeffrey D Hasday
The p38 MAPK family is composed of four kinases of which p38α/MAPK14 is the major proinflammatory member. These kinases contribute to many inflammatory diseases, but the currently available p38 catalytic inhibitors (e.g., SB203580) are poorly effective and cause toxicity. We reasoned that the failure of catalytic p38 inhibitors may derive from their activity against noninflammatory p38 isoforms (e.g., p38β/MAPK11) and loss of all p38α-dependent responses, including anti-inflammatory, counterregulatory responses via mitogen- and stress-activated kinase (MSK) 1/2 and Smad3...
March 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28298523/identification-of-c3b-binding-small-molecule-complement-inhibitors-using-cheminformatics
#18
Brandon L Garcia, D Andrew Skaff, Arindam Chatterjee, Anders Hanning, John K Walker, Gerald J Wyckoff, Brian V Geisbrecht
The complement system is an elegantly regulated biochemical cascade formed by the collective molecular recognition properties and proteolytic activities of more than two dozen membrane-bound or serum proteins. Complement plays diverse roles in human physiology, such as acting as a sentry against invading microorganisms, priming of the adaptive immune response, and removal of immune complexes. However, dysregulation of complement can serve as a trigger for a wide range of human diseases, which include autoimmune, inflammatory, and degenerative conditions...
March 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28298522/scavenger-receptor-marco-orchestrates-early-defenses-and-contributes-to-fungal-containment-during-cryptococcal-infection
#19
Jintao Xu, Adam Flaczyk, Lori M Neal, Zhenzong Fa, Alison J Eastman, Antoni N Malachowski, Daphne Cheng, Bethany B Moore, Jeffrey L Curtis, John J Osterholzer, Michal A Olszewski
The scavenger receptor macrophage receptor with collagenous structure (MARCO) promotes protective innate immunity against bacterial and parasitic infections; however, its role in host immunity against fungal pathogens, including the major human opportunistic fungal pathogen Cryptococcus neoformans, remains unknown. Using a mouse model of C. neoformans infection, we demonstrated that MARCO deficiency leads to impaired fungal control during the afferent phase of cryptococcal infection. Diminished fungal containment in MARCO(-/-) mice was accompanied by impaired recruitment of Ly6C(high) monocytes and monocyte-derived dendritic cells (moDC) and lower moDC costimulatory maturation...
March 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28298521/the-interaction-of-pneumocystis-with-the-c-type-lectin-receptor-mincle-exerts-a-significant-role-in-host-defense-against-infection
#20
Theodore J Kottom, Deanne M Hebrink, Paige E Jenson, Vijayalakshmi Nandakumar, Marcel Wüthrich, Huafeng Wang, Bruce Klein, Sho Yamasaki, Bernd Lepenies, Andrew H Limper
Pneumocystis pneumonia (PCP) remains a major cause of morbidity and mortality within immunocompromised patients. In this study, we examined the potential role of macrophage-inducible C-type lectin (Mincle) for host defense against Pneumocystis Binding assays implementing soluble Mincle carbohydrate recognition domain fusion proteins demonstrated binding to intact Pneumocystis carinii as well as to organism homogenates, and they purified major surface glycoprotein/glycoprotein A derived from the organism. Additional experiments showed that rats with PCP expressed increased Mincle mRNA levels...
March 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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