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Journal of Leukocyte Biology

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https://www.readbyqxmd.com/read/28729360/potential-role-of-cyclophilin-a-in-regulating-cytokine-secretion
#1
REVIEW
Farman Ullah Dawar, Yang Xiong, Muhammad Nasir Khan Khattak, Jun Li, Li Lin, Jie Mei
Cyclophilin A (CypA), a peptidylprolyl cis-trans isomerase, is a ubiquitous and multifunctional protein. In addition to its role as a host-cell receptor for cyclosporine A, CypA has diverse functions in inflammatory conditions and diseases. CypA secreted in response to inflammatory stimuli binds to the cell surface via its receptor CD147 and induces secretion of various inflammatory cytokines. However, silencing and inhibition of either CypA or CD147 inhibits inflammatory cytokine expression and inflammation...
July 20, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28729359/the-%C3%AE-defensin-retrocyclin-101-inhibits-tlr4-and-tlr2-dependent-signaling-and-protects-mice-against-influenza-infection
#2
Daniel Prantner, Kari Ann Shirey, Wendy Lai, Wuyuan Lu, Alexander M Cole, Stefanie N Vogel, Alfredo Garzino-Demo
Despite widespread use of annual influenza vaccines, seasonal influenza-associated deaths number in the thousands each year, in part because of exacerbating bacterial superinfections. Therefore, discovering additional therapeutic options would be a valuable aid to public health. Recently, TLR4 inhibition has emerged as a possible mechanism for protection against influenza-associated lethality and acute lung injury. Based on recent data showing that rhesus macaque θ-defensins could inhibit TLR4-dependent gene expression, we tested the hypothesis that a novel θ-defensin, retrocyclin (RC)-101, could disrupt TLR4-dependent signaling and protect against viral infection...
July 20, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28729358/targeting-c-type-lectin-receptors-a-high-carbohydrate-diet-for-dendritic-cells-to-improve-cancer-vaccines
#3
REVIEW
Dieke van Dinther, Dorian A Stolk, Rieneke van de Ven, Yvette van Kooyk, Tanja D de Gruijl, Joke M M den Haan
There is a growing understanding of why certain patients do or do not respond to checkpoint inhibition therapy. This opens new opportunities to reconsider and redevelop vaccine strategies to prime an anticancer immune response. Combination of such vaccines with checkpoint inhibitors will both provide the fuel and release the brake for an efficient anticancer response. Here, we discuss vaccine strategies that use C-type lectin receptor (CLR) targeting of APCs, such as dendritic cells and macrophages. APCs are a necessity for the priming of antigen-specific cytotoxic and helper T cells...
July 20, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28724696/is-leukostasis-a-crucial-step-or-epiphenomenon-in-the-pathogenesis-of-diabetic-retinopathy
#4
REVIEW
Anne-Eva van der Wijk, John M Hughes, Ingeborg Klaassen, Cornelis J F Van Noorden, Reinier O Schlingemann
Leukostasis in the retinal microvasculature in animal model studies of diabetes is associated with the development of diabetes-like retinopathy. Therefore, it is generally assumed that adhesion of leukocytes is a central event inciting a chronic, low-grade form of inflammation that causes the vascular abnormalities that are specific for the early stages of diabetic retinopathy (DR), which culminate in diabetic macular edema, proliferative DR, and vision loss in humans. Here, we review the literature critically with respect to leukostasis and assess its pathologic consequences in the human diabetic retina...
July 19, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28720687/transcriptional-profiling-reveals-functional-dichotomy-between-human-slan-non-classical-monocytes-and-myeloid-dendritic-cells
#5
Nathalie van Leeuwen-Kerkhoff, Kristina Lundberg, Theresia M Westers, Shahram Kordasti, Hetty J Bontkes, Tanja D de Gruijl, Malin Lindstedt, Arjan A van de Loosdrecht
Human 6-sulfo LacNac-positive (slan(+)) cells have been subject to a paradigm debate. They have previously been classified as a distinct dendritic cell (DC) subset. However, evidence has emerged that they may be more related to monocytes than to DCs. To gain deeper insight into the functional specialization of slan(+) cells, we have compared them with both conventional myeloid DC subsets (CD1c(+) and CD141(+)) in human peripheral blood (PB). With the use of genome-wide transcriptional profiling, as well as functional tests, we clearly show that slan(+) cells form a distinct, non-DC-like population...
July 18, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28720686/oncolytic-virus-induced-cell-death-and-immunity-a-match-made-in-heaven
#6
REVIEW
Jolien De Munck, Alex Binks, Iain A McNeish, Joeri L Aerts
Our understanding of the mechanisms responsible for cancer development has increased enormously over the last decades. However, for many cancers, this has not been translated into a significant improvement in overall survival, and overall mortality remains high. Treatment for many malignancies remains based on surgery, chemotherapy, and radiotherapy. Significant progress has been made toward the development of more specific, more potent, and less invasive treatment modalities, but such targeted therapies remain the exception for most cancers...
July 18, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28716864/alpha1-antitrypsin-binds-hemin-and-prevents-oxidative-activation-of-human-neutrophils-putative-pathophysiological-significance
#7
Sabina Janciauskiene, Srinu Tumpara, Malgorzata Wiese, Sabine Wrenger, Vijith Vijayan, Faikah Gueler, Rongjun Chen, Kukuh Madyaningrana, Ravi Mahadeva, Tobias Welte, Stephan Immenschuh, Joanna Chorostowska-Wynimko
Heme is a ubiquitous compound of human tissues, and it is involved in cellular physiology and metabolism. Once released from the cell, free heme oxidizes to the ferric state (hemin). High levels of hemin can cause oxidative stress and inflammation if not neutralized immediately by specialized scavenger proteins. Human alpha1-antitrypsin (A1AT), an acute-phase glycoprotein and important inhibitor of neutrophil proteases, is also a hemin-binding protein. A short-term exposure of freshly isolated human blood neutrophils to 4 µM hemin results in cell spreading, surface expression of filament protein, vimentin, free radical production, expression of heme oxygenase-1 (HO-1), release of IL-8, and enhanced neutrophil adhesion to human endothelial cells...
July 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28716863/opposing-regulation-and-roles-for-phd3-in-lung-dendritic-cells-and-alveolar-macrophages
#8
Simon J Tavernier, Nele Vanlangenakker, Jessica Vetters, Peter Carmeliet, Sophie Janssens, Bart N Lambrecht
The prolyl hydroxylase domain-containing enzymes (PHDs) are important metabolic sensors of the cell and its environment, which might be employed to alert cells of the immune system. These enzymes regulate the expression of the hypoxia inducible factor (HIF) isoforms and NF-κB, crucial transcription factors controlling cellular metabolism and inflammation. PHD/HIF signaling is activated in the allergic lung and is proposed as a potential druggable pathway. Here, we investigated the regulation and role of the PHD isoforms in CD11c-expressing dendritic cells (DCs) and macrophages (Mϕ), sensors of the environment and crucial antigen-presenting cells in the pathogenesis of asthma...
July 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28698313/hiv-and-hiv-tat-inhibit-lps-induced-il-27-production-in-human-macrophages-by-distinct-intracellular-signaling-pathways
#9
Niranjala Gajanayaka, Shifawn O'Hara, Yulia Konarski, Jason Fernandes, Kar Muthumani, Maya Kozlowski, Jonathan B Angel, Ashok Kumar
Monocyte-derived Mϕs (MDMs) from HIV-infected patients and MDM infected in vitro with HIV exhibit a reduced ability to secrete various cytokines, including IL-12. Recently, IL-27, an IL-12 family cytokine, was shown to inhibit HIV replication in Mϕ. Whether HIV infection or HIV accessory protein(s) impact IL-27 production in Mϕs remains unknown. Herein, we show that in vitro HIV infection, as well as intracellular HIV-Tat (Tat) and Tat peptides, inhibit LPS-induced IL-27 production in human MDMs, suggesting impairment of the TLR4 signaling pathway...
July 11, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28684600/frontline-science-corticotropin-releasing-factor-receptor-subtype-1-is-a-critical-modulator-of-mast-cell-degranulation-and-stress-induced-pathophysiology
#10
Saravanan Ayyadurai, Amelia J Gibson, Susan D'Costa, Elizabeth L Overman, Laura J Sommerville, Ashwini C Poopal, Emily Mackey, Yihang Li, Adam J Moeser
Life stress is a major risk factor in the onset and exacerbation of mast cell-associated diseases, including allergy/anaphylaxis, asthma, and irritable bowel syndrome. Although it is known that mast cells are highly activated upon stressful events, the mechanisms by which stress modulates mast cell function and disease pathophysiology remains poorly understood. Here, we investigated the role of corticotropin-releasing factor receptor subtype 1 (CRF1) in mast cell degranulation and associated disease pathophysiology...
July 6, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28684599/il-23-restoration-of-th17-effector-function-is-independent-of-il-6-and-tgf-%C3%AE-in-a-mouse-model-of-alcohol-and-burn-injury
#11
Xiaoling Li, Abigail R Cannon, Adam M Hammer, Niya L Morris, Mashkoor A Choudhry
T cells play a critical role in host defense against intestinal bacteria. We have shown that ethanol combined with burn injury suppresses Peyer's patch (PP) Th17 cytokines 1 d after injury. We assessed the mechanism of suppressed Th17 effector functions. Mice were gavaged with ethanol 4 h before burn injury and euthanized 1, 3, and 7 d after injury. Mesenteric lymph nodes (MLNs), PPs, and spleen Th1 and Th17 cytokines were assessed. A significant decrease in IL-17, IL-22, IL-2, and IFN-γ were observed in all 3 lymphoid organs 1 and 3 d after injury...
July 6, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28663244/frontline-science-c-myc-regulates-p-selectin-glycoprotein-ligand-1-expression-in-monocytes-during-hiv-1-infection
#12
Ryan Connor, Letitia D Jones, Xing Qiu, Juilee Thakar, Sanjay B Maggirwar
Leukocyte extravasation is a crucial feature of the normal immune response to disease and infection and is implicated in various pathologies during chronic inflammatory disease. P-Selectin glycoprotein ligand-1 (PSGL-1) is critical for leukocyte extravasation; however, despite extensive study, it remains unclear how its expression is regulated, which in turn, impedes a more precise understanding of how its expression level affects transmigration. To investigate the regulation of PSGL-1, 60 subjects, with or without HIV infection, were recruited and PSGL-1 expression in monocytes was measured...
June 29, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28642280/granulocytes-as-modulators-of-dendritic-cell-function
#13
REVIEW
Annelot Breedveld, Tom Groot Kormelink, Marjolein van Egmond, Esther de Jong
Effector T cell development is directly driven by APCs, in particular, by antigen-primed dendritic cells (DCs). Depending on the pathogenic stimulus and the microenvironment, DCs induce proliferation and polarization of naive CD4(+) T cells into different effector subsets, such as Th1, Th2, Th17, or regulatory T cells (Tregs). During inflammation, DCs are found in close proximity to other innate immune cells, including all granulocyte subtypes, which potentially influence the immunomodulatory capacities of DCs...
June 22, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28642279/role-of-myd88-signaling-in-the-imiquimod-induced-mouse-model-of-psoriasis-focus-on-innate-myeloid-cells
#14
Sara Costa, Olivia Marini, Dalila Bevilacqua, Anthony L DeFranco, Baidong Hou, Silvia Lonardi, William Vermi, Pamela Rodegher, Anna Panato, Franco Tagliaro, Clifford A Lowell, Marco A Cassatella, Giampiero Girolomoni, Patrizia Scapini
Psoriasis is a chronic skin disease associated with deregulated activation of immune cells and keratinocytes. In this study, we used the imiquimod (IMQ)-induced mouse model of psoriasis to dissect better the contribution of hematopoietic and skin-resident stromal cells to psoriasis development. The comparison of disease development in mice carrying the hematopoietic cell-specific deletion of MyD88 (Myd88(fl/fl)Vav-cre(+) mice) with mice carrying the total MyD88 deficiency (Myd88(-/-) mice), we show that the progression of skin and systemic inflammation, as well as of epidermal thickening, was completely dependent on MyD88 expression in hematopoietic cells...
June 22, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28642278/rheumatoid-arthritis-and-psoriatic-arthritis-synovial-fluid-stimulates-prolactin-production-by-macrophages
#15
Man Wai Tang, Samuel Garcia, Beatriz Malvar Fernandez, Danielle M Gerlag, Paul-Peter Tak, Kris A Reedquist
Prolactin (PRL) is a neuroendocrine hormone that can promote inflammation. We examined the synovial tissue and fluid levels of PRL in patients with inflammatory arthritis, PRL expression in differentiated Mϕs from patients with arthritis and from healthy donors, and the effects of different stimuli on PRL production by Mϕs. PRL levels were measured in paired synovial fluid (SF) and peripheral blood of patients with rheumatoid arthritis (RA, n = 19), psoriatic arthritis (PsA, n = 11), and gout (n = 11). Synovial-tissue PRL mRNA expression was measured by quantitative PCR in patients with RA (n = 25), PsA (n = 11), and gout (n = 12) and in Mϕs differentiated in SF of patients with RA, PsA, other subtypes of spondyloarthritis (SpA), and gout...
June 22, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28642277/adipose-tissue-macrophages-develop-from-bone-marrow-independent-progenitors-in-xenopus-laevis-and-mouse
#16
Syed F Hassnain Waqas, Anna Noble, Anh C Hoang, Grace Ampem, Manuela Popp, Sarah Strauß, Matthew Guille, Tamás Röszer
ATMs have a metabolic impact in mammals as they contribute to metabolically harmful AT inflammation. The control of the ATM number may have therapeutic potential; however, information on ATM ontogeny is scarce. Whereas it is thought that ATMs develop from circulating monocytes, various tissue-resident Mϕs are capable of self-renewal and develop from BM-independent progenitors without a monocyte intermediate. Here, we show that amphibian AT contains self-renewing ATMs that populate the AT before the establishment of BM hematopoiesis...
June 22, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28637896/technical-advance-new-in-vitro-method-for-assaying-the-migration-of-primary-b-cells-using-an-endothelial-monolayer-as-substrate
#17
Phillip J Stewart-Hutchinson, Taylor P Szasz, Emily R Jaeger, Michael D Onken, John A Cooper, Sharon Celeste Morley
Migration of B cells supports their development and recruitment into functional niches. Therefore, defining factors that control B cell migration will lead to a better understanding of adaptive immunity. In vitro cell migration assays with B cells have been limited by poor adhesion of cells to glass coated with adhesion molecules. We have developed a technique using monolayers of endothelial cells as the substrate for B cell migration and used this technique to establish a robust in vitro assay for B cell migration...
June 21, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28637895/cd4-cd8%C3%AE-double-positive-t-cells-in-skin-draining-lymph-nodes-respond-to-inflammatory-signals-from-the-skin
#18
Nana H Overgaard, Jazmina L Cruz, Jennifer A Bridge, Hendrik J Nel, Ian H Frazer, Nicole L La Gruta, Antje Blumenthal, Raymond J Steptoe, James W Wells
CD4(+)CD8(+) double-positive (DP), mature, peripheral T cells are readily detectable in a variety of species and tissues. Despite a common association with autoimmune and malignant skin disorders, however, little is understood about their role or function. Herein, we show that DP T cells are readily detectable in the blood, spleen, and peripheral lymph nodes of naïve C57BL/6 mice. DP T cells were also present in Jα18(-/-) and CD1d(-/-) mice, indicating that these cells are not NK-T cells. After skin administration of CASAC adjuvant, but not Quil A adjuvant, both total DP T cells and skin-infiltrating DP T cells increased in number...
June 21, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28637894/deep-insight-into-neutrophil-trafficking-in-various-organs
#19
REVIEW
Young-Min Hyun, Chang-Won Hong
Neutrophils are professional phagocytes that constitute the first line of defense in humans. The primary function of neutrophils is to eliminate invading pathogens through oxidative and nonoxidative mechanisms. Because neutrophils rapidly migrate into inflammatory foci via diapedesis and chemotaxis, neutrophil recruitment has long been considered a hallmark of inflammation. Recent advances in intravital microscopic technologies using animal model systems have enabled researchers to directly visualize neutrophil trafficking...
June 21, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28630103/up-regulation-of-ep2-and-ep3-receptors-in-human-tolerogenic-dendritic-cells-boost-the-immunosuppressive-activity-of-pge2
#20
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
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