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Journal of Leukocyte Biology

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https://www.readbyqxmd.com/read/28533357/tlr9-expression-and-secretion-of-lif-by-prostate-cancer-cells-stimulates-accumulation-and-activity-of-polymorphonuclear-mdscs
#1
Haejung Won, Dayson Moreira, Chan Gao, Priyanka Duttagupta, Xingli Zhao, Edwin Manuel, Don Diamond, Yate-Ching Yuan, Zheng Liu, Jeremy Jones, Massimo D'Apuzzo, Sumanta Pal, Marcin Kortylewski
Proinflammatory signals promote prostate tumorigenesis and progression, but their origins and downstream effects remain unclear. We recently demonstrated that the expression of an innate immune receptor, TLR9, by prostate cancer cells is critical for their tumor-propagating potential. We investigated whether cancer cell-intrinsic TLR9 signaling alters composition of the prostate tumor microenvironment. We generated Ras/Myc (RM9) and Myc-driven (Myc-CaP) prostate cancer cells expressing the tetracycline-inducible gene Tlr9 (Tlr9(ON) ) or the control LacZ (LacZ(ON) )...
May 22, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28522600/frontline-science-nasal-epithelial-gm-csf-contributes-to-tlr5-mediated-modulation-of-airway-dendritic-cells-and-subsequent-iga-response
#2
Yuan Cao, Ejuan Zhang, Jingyi Yang, Yi Yang, Jie Yu, Yang Xiao, Wei Li, Dihan Zhou, Yaoming Li, Bali Zhao, Hu Yan, Mengji Lu, Maohua Zhong, Huimin Yan
Flagellin, as a TLR5 agonist, is an established mucosal adjuvant for enhancing mucosal IgA responses by i.n. immunization. Nasal epithelial cells (NECs) are the first sentinel cells to be exposed to antigen and adjuvant in i.n. immunization, and it is suggested that they play an important role in the mucosal adjuvant activity of flagellin. However, the molecular mechanism leading to modulation and the response by flagellin-activated NECs remain unknown. We aimed to identify the soluble mediator(s) from flagellin-activated NECs that modulate the functions of airway dendritic cells (DCs) and enhance subsequent IgA response...
May 18, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28522599/engineering-macrophages-to-eat-cancer-from-marker-of-self-cd47-and-phagocytosis-to-differentiation
#3
REVIEW
Cory Alvey, Dennis E Discher
The ability of a macrophage to engulf and break down invading cells and other targets provides a first line of immune defense in nearly all tissues. This defining ability to "phagos" or devour can subsequently activate the entire immune system against foreign and diseased cells, and progress is now being made on a decades-old idea of directing macrophages to phagocytose specific targets, such as cancer cells. Engineered T cells provide precedence with recent clinical successes against liquid tumors, but solid tumors remain a challenge, and a handful of clinical trials seek to exploit the abundance of tumor-associated macrophages instead...
May 18, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28522598/immunotherapeutic-approaches-of-il-1-neutralization-in-the-tumor-microenvironment
#4
REVIEW
Ron N Apte, Elena Voronov
IL-1 is a pleiotropic cytokine that controls inflammation, immunity, and hemopoiesis. The major IL-1 agonistic molecules are IL-1α and IL-1β, which bind to IL-1R type I (IL-1R1) and induce similar biologic functions. The IL-1R antagonist (IL-1Ra) is a physiologic inhibitor of IL-1R1 signaling. In the tumor microenvironment, IL-1 is expressed by malignant, stromal, and infiltrating cells and supports tumor invasiveness and progression. We have shown that in the tumor microenvironment, the IL-1 agonistic molecules act different as a result of their local amounts and their compartmentalization within the producing cells...
May 18, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28522597/alcohol-aging-and-innate-immunity
#5
REVIEW
Lisbeth A Boule, Elizabeth J Kovacs
The global population is aging: in 2010, 8% of the population was older than 65 y, and that is expected to double to 16% by 2050. With advanced age comes a heightened prevalence of chronic diseases. Moreover, elderly humans fair worse after acute diseases, namely infection, leading to higher rates of infection-mediated mortality. Advanced age alters many aspects of both the innate and adaptive immune systems, leading to impaired responses to primary infection and poor development of immunologic memory. An often overlooked, yet increasingly common, behavior in older individuals is alcohol consumption...
May 18, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28515228/nk1-1-cells-promote-sustained-tissue-injury-and-inflammation-after-trauma-with-hemorrhagic-shock
#6
Shuhua Chen, Rosemary A Hoffman, Melanie Scott, Joanna Manson, Patricia Loughran, Mostafa Ramadan, Anthony J Demetris, Timothy R Billiar
Various cell populations expressing NK1.1 contribute to innate host defense and systemic inflammatory responses, but their role in hemorrhagic shock and trauma remains uncertain. NK1.1(+) cells were depleted by i.p. administration of anti-NK1.1 (or isotype control) on two consecutive days, followed by hemorrhagic shock with resuscitation and peripheral tissue trauma (HS/T). The plasma levels of IL-6, MCP-1, alanine transaminase (ALT), and aspartate aminotransferase (AST) were measured at 6 and 24 h. Histology in liver and gut were examined at 6 and 24 h...
May 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28515227/frontline-science-eosinophil-deficient-mbp-1-and-epx-double-knockout-mice-link-pulmonary-remodeling-and-airways-dysfunction-with-type-2-inflammation
#7
Sergei I Ochkur, Alfred D Doyle, Elizabeth A Jacobsen, William E LeSuer, Wen Li, Cheryl A Protheroe, Katie R Zellner, Dana Colbert, HuaHao H Shen, Charlie G Irvin, James J Lee, Nancy A Lee
Eosinophils and the release of cationic granule proteins have long been implicated in the development of the type 2-induced pathologies linked with respiratory inflammation. Paradoxically, the ablation of the two genes encoding the most abundant of these granule proteins, major basic protein-1 (MBP-1) and eosinophil peroxidase (EPX), results in a near collapse of eosinophilopoiesis. The specificity of this lineage ablation and the magnitude of the induced eosinopenia provide a unique opportunity to clarify the importance of eosinophils in acute and chronic inflammatory settings, as well as to identify potential mechanism(s) of action linked with pulmonary eosinophils in those settings...
May 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28515226/a-neutralizing-anti-g-csfr-antibody-blocks-g-csf-induced-neutrophilia-without-inducing-neutropenia-in-nonhuman-primates
#8
Karen Scalzo-Inguanti, Katherine Monaghan, Kirsten Edwards, Eva Herzog, Danijela Mirosa, Matthew Hardy, Vicki Sorto, Huy Huynh, Steven Rakar, Daria Kurtov, Hal Braley, Nick Wilson, Samantha Busfield, Andrew Nash, Arna Andrews
Neutrophils are the most abundant WBCs and have an essential role in the clearance of pathogens. Tight regulation of neutrophil numbers and their recruitment to sites of inflammation is critical in maintaining a balanced immune response. In various inflammatory conditions, such as rheumatoid arthritis, vasculitis, cystic fibrosis, and inflammatory bowel disease, increased serum G-CSF correlates with neutrophilia and enhanced neutrophil infiltration into inflamed tissues. We describe a fully human therapeutic anti-G-CSFR antibody (CSL324) that is safe and well tolerated when administered via i...
May 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28515225/energy-metabolic-pathways-control-the-fate-and-function-of-myeloid-immune-cells
#9
REVIEW
Amir A Al-Khami, Paulo C Rodriguez, Augusto C Ochoa
The past decade has seen a significant interest in investigating the intracellular metabolism of cells of the immune system. This has increased the realization that immune cells endure metabolic reprogramming upon responding to pathogen-derived or inflammatory signals. More importantly, not only does this metabolic switch provide for the bioenergetic and biosynthetic demands but also it, in a highly specific manner, determines the cellular fate and function. In this review, we discuss the metabolic aspects that regulate the differentiation and function of myeloid cells, pivotal for both innate and adaptive immunity...
May 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28495790/systemic-inflammatory-response-syndrome-related-lymphopenia-is-associated-with-adenosine-a1-receptor-dysfunction
#10
Reut Riff, Yair Cohen, Hadar Eini-Rider, Oshri Naamani, Julia Mazar, Yosef S Haviv, Cidio Chaimovitz, Amos Douvdevani
SIRS is associated with lymphopenia, and prolonged lymphopenia of septic patients has been associated with increased mortality risk. We hypothesize that elevated adenosine during SIRS down-regulates Gi-coupled A1R, which signals an effect that sensitizes a cAMP-dependent lymphotoxic response. In this study, we evaluate the role of adenosine in SIRS-mediated lymphopenia and impaired IL-15 production. Cecal ligation and puncture was used to induce sepsis-associated SIRS in mice. BMDCs were cultured and used to measure the effect of adenosine on IL-15...
May 11, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28495789/dietary-nondigestible-oligosaccharides-and-bifidobacterium-breve-m-16v-suppress-allergic-inflammation-in-intestine-via-targeting-dendritic-cell-maturation
#11
Sander de Kivit, Atanaska I Kostadinova, JoAnn Kerperien, Mary E Morgan, Veronica Ayechu Muruzabal, Gerard A Hofman, Leon M J Knippels, Aletta D Kraneveld, Johan Garssen, Linette E M Willemsen
Dietary intervention with short-chain galacto-oligosaccharides (scGOS), long-chain fructo-oligosaccharides (lcFOS) and Bifidobacterium breve M-16V (Bb) (GF/Bb) suppresses food allergic symptoms in mice, potentially via intestinal epithelial cell (IEC)-derived galectin-9. Furthermore, in vitro studies showed galacto- and fructo-oligosaccharides (GF) to enhance the immunomodulatory capacity of a TLR9 ligand representing bacterial CpG DNA when exposed to IEC. In this study, we investigated whether GF/Bb modulates dendritic cells (DCs) and subsequent Th2 and regulatory T cell (Treg) frequency in the small intestinal lamina propria (SI-LP)...
May 11, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28476751/frontline-science-myeloid-cell-specific-deletion-of-cebpb-decreases-sepsis-induced-immunosuppression-in-mice
#12
Melissa B McPeak, Dima Youssef, Danielle A Williams, Christopher L Pritchett, Zhi Q Yao, Charles E McCall, Mohamed El Gazzar
Sepsis inflammation accelerates myeloid cell generation to compensate for rapid mobilization of the myeloid progenitors from bone marrow. This inflammation-driven myelopoiesis, however, generates myeloid progenitors with immunosuppressive functions that are unable to differentiate into mature, innate immune cells. The myeloid-derived suppressor cells (MDSCs) expand markedly in the later phases of sepsis, suppress both innate and adaptive immunity, and thus, elevate mortality. Using a murine model with myeloid-restricted deletion of the C/EBPβ transcription factor, we show that sepsis-induced generation of MDSCs depends on C/EBPβ...
May 5, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28476750/programming-and-memory-dynamics-of-innate-leukocytes-during-tissue-homeostasis-and-inflammation
#13
REVIEW
Christina Lee, Shuo Geng, Yao Zhang, Allison Rahtes, Liwu Li
The field of innate immunity is witnessing a paradigm shift regarding "memory" and "programming" dynamics. Past studies of innate leukocytes characterized them as first responders to danger signals with no memory. However, recent findings suggest that innate leukocytes, such as monocytes and neutrophils, are capable of "memorizing" not only the chemical nature but also the history and dosages of external stimulants. As a consequence, innate leukocytes can be dynamically programmed or reprogrammed into complex inflammatory memory states...
May 5, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28465448/elevated-interferon-%C3%AE-induced-protein-10-and-its-receptor-cxcr3-impair-nk-cell-function-during-hiv-infection
#14
Zhuo Wang, Tong Wu, Meichen Ma, Zining Zhang, Yajing Fu, Jing Liu, Junjie Xu, Haibo Ding, Xiaoxu Han, Zhenxing Chu, Yuntao Wu, Hong Shang, Yongjun Jiang
As the first line of defense in the human immune system, NK cells play essential roles in prevention of tumorigenesis and viral infection. It is known that NK cells have impaired function in HIV infection; however, it remains unclear why this occurs. IP-10 is a chemokine and inflammatory factor that is associated with such diseases as tuberculosis, hepatitis B virus, and pancreatic cancer. The aim of this study was to evaluate IP-10 levels and CXCR3 expression in NK cells that were affected by HIV and to elucidate whether NK cell function could be affected by IP-10...
May 2, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28465447/human-blood-monocytes-are-able-to-form-extracellular-traps
#15
Vanessa Granger, Dorothée Faille, Vanessa Marani, Benoît Noël, Yann Gallais, Natacha Szely, Héloïse Flament, Marc Pallardy, Sylvie Chollet-Martin, Luc de Chaisemartin
Neutrophil extracellular traps (NETs) are extracellular DNA filaments formed during neutrophil activation. This process, called netosis, was originally associated with neutrophil antibacterial properties. However, several lines of evidence now suggest a major role for netosis in thrombosis, autoimmune diseases, and cancer. We demonstrate here that highly purified human blood monocytes are also capable of extracellular trap (ET) release in response to several stimuli. Monocyte ETs display a morphology analogous to NETs and are associated with myeloperoxidase (MPO), lactoferrin (LF), citrullinated histones, and elastase...
May 2, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28432083/optimal-cd4-t-cell-priming-after-lps-based-adjuvanticity-with-cd134-costimulation-relies-on-cxcl9-production
#16
Paurvi Shinde, Wenhai Liu, Antoine Ménoret, Andrew D Luster, Anthony T Vella
LPS is a powerful adjuvant, and although LPS-mediated TLR4 signaling has been exquisitely delineated, the in vivo mechanism of how TLR4 responses impact T cell priming is far less clear. Besides costimulation, TNF and type 1 IFN are dominant cytokines released after TLR4 activation and can shape T cell responses, but other downstream factors have not been examined extensively. Depending on context, we show that IFNαR1 blockade resulted in minor to major effects on specific CD4 T cell clonal expansion. To help explain these differences, it was hypothesized that IFNαR1 blockade would inhibit specific T cell migration by reducing chemokine receptor signaling, but specific CD4 T cells from IFNαR1-blocked mice were readily able to migrate in response to specific chemokines...
April 21, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28428201/dihydrolipoamide-dehydrogenase-lpd-rv0462-specific-t-cell-recall-responses-are-higher-in-healthy-household-contacts-of-tb-a-novel-immunodominant-antigen-from-m-tuberculosis
#17
Santhi Devasundaram, Alamelu Raja
The partial effectiveness against pulmonary tuberculosis (PTB), displayed by the existing tuberculosis (TB) vaccine, bacillus Calmette-Guérin (BCG), highlights the need for novel vaccines to replace or improve BCG. In TB immunology, antigen-specific cellular immune response is frequently considered indispensable. Latency-associated antigens are intriguing as targets for TB vaccine development. The mycobacterial protein, dihydrolipoamide dehydrogenase (Lpd; Rv0462), the third enzyme of the pyruvate dehydrogenase (PDH) complex, facilitates Mycobacterium tuberculosis to resist host reactive nitrogen intermediates...
April 20, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28411215/the-effect-of-rho-drugs-on-mast-cell-activation-and-degranulation
#18
Avinash Sheshachalam, Alicia Baier, Gary Eitzen
Mast cells are tissue-resident immune cells that produce potent proinflammatory mediators, which are stored in cytoplasmic granules. Stimulation triggers degranulation, a process that mobilizes granules to dock and fuse to the plasma membrane, releasing mediators. Mast cell degranulation has an important role in immunity but can also intensify inflammation and contribute to allergic disorders. Hence, it is important to understand signaling pathways that regulate mast cell degranulation. Here, we examined the role of Rho proteins in regulating mast cell activation leading to degranulation...
April 14, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28408397/the-il-31-il-31-receptor-axis-general-features-and-role-in-tumor-microenvironment
#19
REVIEW
Elisa Ferretti, Anna Corcione, Vito Pistoia
IL-31 is a recently identified cytokine with a well-defined role in the pathogenesis of pruritus. IL-31, whose production is induced by IL-4 and IL-33, binds a heterodimeric receptor (R) composed of the exclusive IL-31RA chain and the shared oncostatin M R. Signaling through the IL-31R involves the MAPK, PI3K/AKT and Jak/STAT pathways. Different variants and isoforms of IL-31RA with different signaling activities have been identified. IL-31 is produced predominantly by circulating Th2 lymphocytes and skin-homing CLA(+)CD45RO(+) T cells...
April 13, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28408396/novel-role-of-immature-myeloid-cells-in-formation-of-new-lymphatic-vessels-associated-with-inflammation-and-tumors
#20
REVIEW
Sophia Ran, Andrew Wilber
Inflammation triggers an immune cell-driven program committed to restoring homeostasis to injured tissue. Central to this process is vasculature restoration, which includes both blood and lymphatic networks. Generation of new vessels or remodeling of existing vessels are also important steps in metastasis-the major cause of death for cancer patients. Although roles of the lymphatic system in regulation of inflammation and cancer metastasis are firmly established, the mechanisms underlying the formation of new lymphatic vessels remain a subject of debate...
April 13, 2017: Journal of Leukocyte Biology
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