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Journal of Leukocyte Biology

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https://www.readbyqxmd.com/read/28630103/up-regulation-of-ep2-and-ep3-receptors-in-human-tolerogenic-dendritic-cells-boost-the-immunosuppressive-activity-of-pge2
#1
Georgina Flórez-Grau, Raquel Cabezón, Kyra J E Borgman, Carolina España, Juan Jose Lozano, Maria F Garcia-Parajo, Daniel Benítez-Ribas
Dendritic cells (DCs) are APCs essential in regulating the immune response. PGE2, produced during inflammation, has a pivotal role in the maturation of DCs and, therefore, is vital for the immune response. The large variety of biologic functions governed by PGE2 is mediated by its signaling through 4 distinct E-type prostanoid (EP) receptors. Immunogenic DCs express EP2 and EP4, which mediate the PGE2 signaling. However, the expression and function of EP receptors in human tolerogenic DCs (tol-DCs), which present an inhibitory phenotype, have not yet, to our knowledge, been assessed...
June 19, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28630102/the-phenotype-and-function-of-preterm-infant-monocytes-implications-for-susceptibility-to-infection
#2
REVIEW
Emma de Jong, Tobias Strunk, David Burgner, Pascal M Lavoie, Andrew Currie
The extreme vulnerability of preterm infants to invasive microbial infections has been attributed to "immature" innate immune defenses. Monocytes are important innate immune sentinel cells critical in the defense against infection in blood. They achieve this via diverse mechanisms that include pathogen recognition receptor- and inflammasome-mediated detection of microbes, migration into infected tissues, and differentiation into Mϕs and dendritic cells, initiation of the inflammatory cascade by free radicals and cytokine/chemokine production, pathogen clearance by phagocytosis and intracellular killing, and the removal of apoptotic cells...
June 19, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28626046/perpetual-change-autophagy-the-endothelium-and-response-to-vascular-injury
#3
REVIEW
Ulka Sachdev, Michael T Lotze
Current studies of vascular health, aging, and autophagy emphasize how the endothelium adapts to stress and contributes to disease. The endothelium is far from an inert barrier to blood-borne cells, pathogens, and chemical signals; rather, it actively translates circulating mediators into tissue responses, changing rapidly in response to physiologic stressors. Macroautophagy-the cellular ingestion of effete organelles and protein aggregates to provide anabolic substrates to fuel bioenergetics in times of stress-plays an important role in endothelial cell homeostasis, vascular remodeling, and disease...
June 16, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28619950/how-neutrophils-resist-shear-stress-at-blood-vessel-walls-molecular-mechanisms-subcellular-structures-and-cell-cell-interactions
#4
REVIEW
Daniela Begandt, Sarah Thome, Markus Sperandio, Barbara Walzog
Neutrophils are the first cells arriving at sites of tissue injury or infection to combat invading pathogens. Successful neutrophil recruitment to sites of inflammation highly depends on specific molecular mechanisms, fine-tuning the received information into signaling pathways and converting them into well-described recruitment steps. This review highlights the impact of vascular flow conditions on neutrophil recruitment and the multitude of mechanisms developed to enable this sophisticated process under wall shear stress conditions...
June 15, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28619949/expansion-and-activation-of-granulocytic-myeloid-derived-suppressor-cells-in-childhood-precursor-b-cell-acute-lymphoblastic-leukemia
#5
Yu-Feng Liu, Ying-Ying Chen, Ying-Yi He, Jia-Yi Wang, Jian-Ping Yang, Shu-Ling Zhong, Nan Jiang, Pan Zhou, Hua Jiang, Jie Zhou
Precursor B cell acute lymphoblastic leukemia (B-ALL) is a B cell-derived, malignant disorder with the highest incidence among children. In addition to the genetic abnormality, a dysregulated immune system also has an important role in the pathogenesis of B-ALL. Myeloid-derived suppressor cells (MDSCs) represent one of the key drivers in immune tolerance against tumor cells, including various solid tumors and hematologic malignancies. The role of MDSCs in B-ALL remains poorly understood. Here, we showed that the granulocytic (G)-MDSC population was significantly elevated in both the peripheral blood and BM of patients with B-ALL, when compared with age-matched healthy controls...
June 15, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28619948/administration-of-immunobiotic-lactobacillus-plantarum-delays-but-does-not-prevent-lethal-pneumovirus-infection-in-rag1-mice
#6
Caroline M Percopo, Michelle Ma, Helene F Rosenberg
Administration of immunobiotic Lactobacillus plantarum (Lp) directly to the respiratory mucosa promotes cross-protection against lethal pneumovirus infection via B-cell-independent mechanisms. In this study, we examined Lp-mediated cross protection in Rag1(-/-) mice which cannot clear virus from lung tissue. Although Lp was initially protective, Rag1(-/-) mice ultimately succumbed to a delayed lethal outcome associated with local production of the proinflammatory cytokines CCL1, -2, and -7, granulocyte recruitment, and ongoing virus replication...
June 15, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28606940/shp1-function-in-myeloid-cells
#7
REVIEW
Clare L Abram, Clifford A Lowell
The motheaten mouse was first described in 1975 as a model of systemic inflammation and autoimmunity, as a result of immune system dysregulation. The phenotype was later ascribed to mutations in the cytoplasmic tyrosine phosphatase Shp1. This phosphatase is expressed widely throughout the hematopoietic system and has been shown to impact a multitude of cell signaling pathways. The determination of which cell types contribute to the different aspects of the phenotype caused by global Shp1 loss or mutation and which pathways within these cell types are regulated by Shp1 is important to further our understanding of immune system regulation...
June 12, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28606939/transcriptional-and-epigenetic-regulation-of-t-cell-hyporesponsiveness
#8
REVIEW
Renata M Pereira, Patrick G Hogan, Anjana Rao, Gustavo J Martinez
Naive CD8(+) T cells differentiate into effector and memory cytolytic T cells (CTLs) during an acute infection. In contrast, in scenarios of persistent antigen stimulation, such as chronic infections and cancer, antigen-specific CTLs show a gradual decrease in effector function, a phenomenon that has been termed CD8(+) T cell "exhaustion" or "dysfunction." Another hyporesponsive state, termed anergy, is observed when T cells are activated in the absence of positive costimulatory signals. Among the many negative regulators induced in hyporesponsive T cells are inhibitory cell-surface receptors, such as PD-1, LAG-3, CTLA-4, and TIM-3; "checkpoint blockade" therapies that involve treatment of patients with cancer with blocking antibodies to those receptors show considerable promise in the clinic because the blocking antibodies can mitigate hyporesponsiveness and promote tumor rejection...
June 12, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28606938/peptide-mediated-mast-cell-activation-ligand-similarities-for-receptor-recognition-and-protease-induced-regulation
#9
REVIEW
Lei Lu, Marianna Kulka, Larry D Unsworth
MCs are crucial regulators of the innate immune response. MC degranulation is a rapid response mechanism that allows for the release of a stored plethora of inflammatory mediators, including histamine, heparin, various serine proteases, chemokines, and cytokines. The activation of MCs can lead to the de novo expression of a variety of chemokines and cytokines that can influence a variety of outcomes: inflammation, angiogenesis, and others. A variety of IgE-independent mediators, including IgG, cytokines, chemokines, exogenous molecules, drugs, and cationic peptides, and others, can directly trigger MC activation...
June 12, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28600306/expression-of-lewis-a-glycans-on-polymorphonuclear-leukocytes-augments-function-by-increasing-transmigration
#10
Jennifer C Brazil, Ronen Sumagin, Sean R Stowell, Goo Lee, Nancy A Louis, Richard D Cummings, Charles A Parkos
PMN-expressed fucosylated glycans from the Lewis glycan family, including Lewis-x (Le(x)) and sialyl Lewis-x (sLe(x)), have previously been implicated in the regulation of important PMN functions, including selectin-mediated trafficking across vascular endothelium. Although glycans, such as Le(x) and sLe(x), which are based on the type 2 sequence (Galβ1-4GlcNAc-R), are abundant on PMNs, the presence of type 1 Galβ1-3GlcNAc-R glycans required for PMN expression of the closely related stereoisomer of Le(x), termed Lewis-A (Le(a)), has not, to our knowledge, been reported...
June 9, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28596252/success-in-bone-marrow-failure-novel-therapeutic-directions-based-on-the-immune-environment-of-myelodysplastic-syndromes
#11
REVIEW
Alyssa H Cull, Michael J Rauh
Myelodysplastic syndromes (MDS) are clonal neoplasms of aging that are associated with BM failure, related cytopenias, fatigue, susceptibility to infections, bruising, bleeding, a shortened lifespan, and a propensity for leukemic transformation. Most frail, elderly patients are not candidates for curative allogeneic BM transplantations and instead receive expectant management, supportive blood transfusions, or empirical, nontargeted therapy. It has been known for some time that MDS arises in an abnormal BM immune environment; however, connections have only recently been established with recurring MDS-associated mutations...
June 8, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28588029/tgf-%C3%AE-inhibits-il-7-induced-proliferation-in-memory-but-not-naive-human-cd4-t-cells
#12
Thao P Nguyen, Scott F Sieg
TGF-β is a potent suppressor of T cell activation and expansion. Although the antiproliferative effects of TGF-β are well characterized in TCR-activated cells, the effects of TGF-β on T cell proliferation driven by homeostatic cytokines, such as IL-7, are poorly defined. In the current study, we found that TGF-β inhibits IL-7-induced proliferation in memory, but not in naive human CD4(+) T cells. TGF-β impaired c-myc induction in all CD4(+) T cell maturation subsets, although the impairment was less sustained in naive CD4(+) T cells...
June 6, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28584078/alcohol-induced-mir-155-and-hdac11-inhibit-negative-regulators-of-the-tlr4-pathway-and-lead-to-increased-lps-responsiveness-of-kupffer-cells-in-alcoholic-liver-disease
#13
Shashi Bala, Timea Csak, Karen Kodys, Donna Catalano, Aditya Ambade, Istvan Furi, Patrick Lowe, Yeonhee Cho, Arvin Iracheta-Vellve, Gyongyi Szabo
Inflammation promotes the progression of alcoholic liver disease. Alcohol sensitizes KCs to gut-derived endotoxin (LPS); however, signaling pathways that perpetuate inflammation in alcoholic liver disease are only partially understood. We found that chronic alcohol feeding in mice induced miR-155, an inflammatory miRNA in isolated KCs. We hypothesized that miR-155 might increase the responsiveness of KCs to LPS via targeting the negative regulators of LPS signaling. Our results revealed that KCs that were isolated from alcohol-fed mice showed a decrease in IRAK-M, SHIP1, and PU...
June 5, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28584077/vascular-sprouts-induce-local-attraction-of-proangiogenic-neutrophils
#14
Gustaf Christoffersson, Jalal Lomei, Paul O'Callaghan, Johan Kreuger, Stefan Engblom, Mia Phillipson
Angiogenesis, the growth of new blood vessels, is a complex process requiring the orchestration of numerous different cell types, growth factors, and chemokines. Some of the recently acknowledged actors in this process are immune cells. They accumulate at hypoxic sites, but the kinetics, dynamics, and regulation of that trafficking are unknown. In this study, we used intravital and live cell imaging to understand how neutrophils and macrophages migrate and behave at angiogenic sites. We developed two reproducible models of angiogenesis: one by transplanting isolated and hypoxic pancreatic islets into the cremaster muscles of mice, and another by in vitro coculturing of mouse aortic rings with neutrophils...
June 5, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28584076/frontline-science-aspirin-triggered-resolvin-d1-controls-herpes-simplex-virus-induced-corneal-immunopathology
#15
Naveen K Rajasagi, Siddheshvar Bhela, Siva Karthik Varanasi, Barry T Rouse
Stromal keratitis (SK) is a chronic immunopathological lesion of the eye, caused by HSV-1 infection, and a common cause of vision impairment in humans. The inflammatory lesions in the cornea are primarily caused by neutrophils with the active participation of CD4(+) T cells. Therefore, the targeting of these immune cell types and their products represents a potentially valuable form of therapy to reduce the severity of disease. Resolvin D1 (RvD1) and its epimer aspirin-triggered RvD1 (AT-RvD1) are lipid mediators derived from docosahexaenoic acid (DHA) and were shown to promote resolution in several inflammatory disease models...
June 5, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28550123/essential-role-for-histone-deacetylase-11-hdac11-in-neutrophil-biology
#16
Eva Sahakian, Jie Chen, John J Powers, Xianghong Chen, Kamira Maharaj, Susan L Deng, Maritza Lienlaf, Hong Wei Wang, Fengdong Cheng, Andressa L Sodré, Allison Distler, Limin Xing, Patricio Perez-Villarroel, Sheng Wei, Alejandro Villagra, Ed Seto, Eduardo M Sotomayor, Pedro Horna, Javier Pinilla-Ibarz
Epigenetic changes in chromatin structure have been recently associated with the deregulated expression of critical genes in normal and malignant processes. HDAC11, the newest member of the HDAC family of enzymes, functions as a negative regulator of IL-10 expression in APCs, as previously described by our lab. However, at the present time, its role in other hematopoietic cells, specifically in neutrophils, has not been fully explored. In this report, for the first time, we present a novel physiologic role for HDAC11 as a multifaceted regulator of neutrophils...
May 26, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28550122/the-blood-borne-sialyltransferase-st6gal-1-is-a-negative-systemic-regulator-of-granulopoiesis
#17
Christopher W L Dougher, Alexander Buffone, Michael J Nemeth, Mehrab Nasirikenari, Eric E Irons, Paul N Bogner, Joseph T Y Lau
Responding to systemic demands in producing and replenishing end-effector blood cells is predicated on the appropriate delivery and interpretation of extrinsic signals to the HSPCs. The data presented herein implicate the systemic, extracellular form of the glycosyltransferase ST6Gal-1 in the regulation of late-stage neutrophil development. ST6Gal-1 is typically a membrane-bound enzyme sequestered within the intracellular secretory apparatus, but an extracellular form is released into the blood from the liver...
May 26, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28550121/bcl6-represses-antiviral-resistance-in-follicular-t-helper-cells
#18
Tohti Amet, Young Min Son, Li Jiang, In Su Cheon, Su Huang, Samir K Gupta, Alexander L Dent, Luis J Montaner, Qigui Yu, Jie Sun
Follicular Th (Tfh) cells are a distinct subset of Th cells that help B cells produce class-switched antibodies. Studies have demonstrated that Tfh cells are highly prone to HIV infection and replication. However, the molecular mechanisms underlying this phenomenon are largely unclear. Here, we show that murine and human Tfh cells have diminished constitutive expression of IFN-stimulated genes (ISGs) inclusive of antiviral resistance factor MX dynamin-like GTPase 2 (MX2) and IFN-induced transmembrane 3 (IFITM3) compared with non-Tfh cells...
May 26, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28550120/hiv-1-decreases-nrf2-are-activity-and-phagocytic-function-in-alveolar-macrophages
#19
Bashar S Staitieh, Lingmei Ding, Wendy A Neveu, Paul Spearman, David M Guidot, Xian Fan
Respiratory complications occur frequently in individuals living with human immunodeficiency-1 virus (HIV) infection, and there is evidence that HIV-related oxidative stress impairs alveolar macrophage immune function. We hypothesized that nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a master transcription factor that activates the antioxidant response element (ARE) and regulates antioxidant defenses, has an important role in alveolar macrophage (AMs) immune dysfunction in individuals with HIV infections...
May 26, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28550119/francisella-novicida-inhibits-spontaneous-apoptosis-and-extends-human-neutrophil-lifespan
#20
Lauren C Kinkead, Drew C Fayram, Lee-Ann H Allen
Francisella novicida is a Gram-negative bacterium that is closely related to the highly virulent facultative intracellular pathogen, Francisella tularensis Data published by us and others demonstrate that F. tularensis virulence correlates directly with its ability to impair constitutive apoptosis and extend human neutrophil lifespan. In contrast, F. novicida is attenuated in humans, and the mechanisms that account for this are incompletely defined. Our published data demonstrate that F. novicida binds natural IgG that is present in normal human serum, which in turn, elicits NADPH oxidase activation that does not occur in response to F...
May 26, 2017: Journal of Leukocyte Biology
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