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Journal of Leukocyte Biology

Zhenwu Luo, Zejun Zhou, Elizabeth Ogunrinde, Tao Zhang, Zhen Li, Lisa Martin, Zhuang Wan, Hao Wu, Zhiqiang Qin, Tongwen Ou, Jiafeng Zhang, Lei Ma, Guoyang Liao, Sonya Heath, Lei Huang, Wei Jiang
Although effective antiretroviral therapy (ART) suppresses HIV viral replication, prevents AIDS-related complications, and prolongs life, a proportion of patients fails to restore the patients' CD4(+) T cell number to the level of healthy individuals. Increased mortality and morbidity have been observed in these patients. In the current study, we have investigated the role of auto-IgGs in CD4(+) T cell apoptosis and recovery in a cross-sectional study. All HIV(+) subjects were on viral-suppressive ART treatment with a different degree of CD4(+) T cell reconstitution...
October 13, 2017: Journal of Leukocyte Biology
Aggasit Manosudprasit, Alpdogan Kantarci, Hatice Hasturk, Danielle Stephens, Thomas E Van Dyke
The purpose of this study was to test the hypothesis that peripheral blood neutrophils (PMN) exhibit delayed spontaneous apoptosis in individuals with diabetes mellitus type 2 (T2DM) and that the delay is exacerbated further among people who coexpress chronic periodontitis (CP). Seventy-three individuals were enrolled, including those with T2DM (n = 16), CP (n = 15), T2DM + CP (n = 21), and healthy volunteers (n = 21). PMN apoptosis was determined by flow cytometry using TUNEL and Annexin V assays. The activity of caspase-3, -8, and -9 was measured by colorimetric assay...
October 11, 2017: Journal of Leukocyte Biology
Debra A Tokarz, Amy K Heffelfinger, Dereje D Jima, Jamie Gerlach, Radhika N Shah, Ivan Rodriguez-Nunez, Amanda N Kortum, Ashley A Fletcher, Shila K Nordone, J McHugh Law, Steffen Heber, Jeffrey A Yoder
The vertebrate immune response comprises multiple molecular and cellular components that interface to provide defense against pathogens. Because of the dynamic complexity of the immune system and its interdependent innate and adaptive functionality, an understanding of the whole-organism response to pathogen exposure remains unresolved. Zebrafish larvae provide a unique model for overcoming this obstacle, because larvae are protected against pathogens while lacking a functional adaptive immune system during the first few weeks of life...
October 11, 2017: Journal of Leukocyte Biology
Chiara Ripamonti, Angela Papagna, Claudio Storini, Daniela Miglietta, Maria Foti
NO mediates a variety of physiologic processes and is considered an important intracellular messenger in different cellular systems. Because of its complex regulation and multiple molecular and cellular targets, NO provides both stimulatory and suppressive properties in the immune system. Dendritic cells (DCs) are considered the most potent APCs, whose regulation has important implications in the induction of an effective immune response. In this study, we analyzed the effect of the compound NCX 2057, a new class of NO-releasing derivatives of ferulic acid, on activation and functional properties of DCs...
October 11, 2017: Journal of Leukocyte Biology
Zheng Pang, Robert D Junkins, Adam J MacNeil, Craig McCormick, Zhenyu Cheng, Wei-Min Chen, Tong-Jun Lin
Infection with the opportunistic pathogen Pseudomonas aeruginosa is effectively controlled through tightly coordinated inflammation in healthy individuals. Dysregulated inflammation in cystic fibrosis greatly increases susceptibility to P. aeruginosa and lung damage. Recently, we identified regulator of calcineurin-1, a small, conserved protein that suppresses the NFAT pathway by inhibition of calcineurin and functions as a central negative regulator of multiple inflammatory transcription factors after P. aeruginosa lung infection, implying a role for the canonical NFAT pathway in P...
October 10, 2017: Journal of Leukocyte Biology
Mihai G Netea, Leo A B Joosten, Jos W M van der Meer
Cancer immunotherapy has steadily progressed during the past decades, with checkpoint inhibitor therapy becoming the latest and one of the most promising treatments. Despite the progress, most of the patients do not respond or develop resistance, and novel additional approaches are needed to improve the clinical effectiveness of immunotherapy. Trained immunity (TI) has been described recently as a process of epigenetic and metabolic reprogramming that induces a long-term enhanced function of innate immune cells...
October 10, 2017: Journal of Leukocyte Biology
Adam G Peres, Robert Zamboni, Irah L King, Joaquín Madrenas
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that triggers a broad response, which includes the regulation of proinflammatory cytokine production by monocytes and macrophages. AHR is negatively regulated by a set of genes that it transcriptionally activates, including the AHR repressor (Ahrr) and the cytochrome P450 1 (Cyp1) family, which are critical for preventing exacerbated AHR activity. An imbalance in these regulatory mechanisms has been shown to cause severe defects in lymphoid cells...
October 10, 2017: Journal of Leukocyte Biology
Jiasheng Wang, Yongxian Hu, He Huang
CART19 therapy has revolutionized the treatment of CD19(+) acute lymphoblastic leukemia, demonstrating an unprecedented complete remission rate; however, as follow-up prolongs, a high relapse rate after CART19 therapy has emerged as one of the major problems. Relapse can be attributed to the loss of leukemic cell immunogenicity, diminished function and amount of CART19 cells, and the inhibitory bone marrow microenvironment. Although studies to prevent and treat relapse have begun, some encouraging results have demonstrated the possibility of decreasing the relapse rate...
October 10, 2017: Journal of Leukocyte Biology
Yin Luo, Xiaoyan Xie, Di Luo, Yuan Wang, Yijun Gao
Fibrosis, which can be defined as an abnormal or excessive accumulation of extracellular matrix (ECM), particularly fibrillar collagens, is a key driver of progressive organ dysfunction in many inflammatory and metabolic diseases, including idiopathic pulmonary fibrosis (IPF), cirrhosis, nephropathy, and oral submucous fibrosis (OSF). It has been estimated to contribute to ∼45% of deaths in the developed world. Therefore, agents that target specific fibrotic pathways, with the consequence of slowing, arresting, or even reversing the progression of tissue fibrogenesis, are urgently needed...
October 6, 2017: Journal of Leukocyte Biology
Magali Humbert, Elena A Federzoni, Mario P Tschan
We have previously demonstrated that the death-associated protein kinase 2 (DAPK2) expression is significantly reduced in acute myeloid leukemia (AML), particularly in acute promyelocytic leukemia (APL) blast cells. In this study, we aimed at further understanding DAPK2 function and regulation during arsenic trioxide (ATO) cytotoxic or all-trans retinoic acid (ATRA) differentiation therapy in APL cells. We found that the p53 family member transactivation domain-p73 isoform (TAp73) binds to and activates the DAPK2 promoter, whereas the dominant-negative ΔNp73 isoform inhibits DAPK2 transcription...
October 4, 2017: Journal of Leukocyte Biology
Youngrok Park, Joon Lee, Jae-Yong Kwak, Kyoungmi Noh, Eunjung Yim, Hyun-Kyung Kim, Young June Kim, Hal E Broxmeyer, Jeong-A Kim
We report the unique role of CX3CL1 (or fractalkine) on CD11b(+) myelomonocytic cells expressing CX3CR1, the only known receptor for CX3CL1, in promoting blood perfusion recovery. In a mouse ischemic hind-limb model, CD11b(+)CX3CR1(+) cells migrated to ischemic femoral muscles through CX3CL1-mediated chemotaxis. CD11b(+)CX3CR1(+) macrophages isolated from ischemic tissues [tissue (T)-CD11b(+)CX3CR1(+)] of muscle exert a proangiogenic effect through platelet factor-4 (CXCL4; PF-4) production. PF-4 does not promote angiogenesis by itself but, instead, increases VEGF-mediated angiogenesis...
October 4, 2017: Journal of Leukocyte Biology
Jeroen D Langereis, Peter Pickkers, Stan de Kleijn, Jelle Gerretsen, Marien I de Jonge, Matthijs Kox
The immune inhibitory checkpoint molecule programmed death ligand (PD-L)-1 is increasingly recognized as an important player in the immune suppression observed in patients with sepsis, but its role has mainly been studied in monocytes. In an earlier study, we demonstrated that experimental human endotoxemia results in mobilization of a subset of PD-L1-expressing neutrophils displaying an IFN-γ-induced transcriptome profile. Herein, we identify the source of IFN-γ production during murine endotoxemia and its role in the generation of PD-L1(+)-suppressive neutrophils...
October 3, 2017: Journal of Leukocyte Biology
Anthony J Sadler
IFNs protect us against infection from viral pathogens, but can also induce damaging inflammation and are associated with the development of autoimmune conditions. By dissecting the response that is mediated by different IFN-regulated genes, we hoped to identify targets that will enable us to preserve the defense against pathogens while minimizing immune disease. Toward this, several reports have identified that variability in the gene that encodes the melanoma differentiation-associated protein (MDA)-5 and other molecules in this pathway correlated with the risk of autoimmune diseases...
October 3, 2017: Journal of Leukocyte Biology
Amiran Dzutsev, Alison Hogg, Yongjun Sui, Shahram Solaymani-Mohammadi, Huifeng Yu, Blake Frey, Yichuan Wang, Jay A Berzofsky
Mechanisms that imprint T cell homing to the small intestine have been well studied; however, those for homing to the colon are poorly understood. Recently, we found that these are distinct subcompartments of the gut mucosal immune system, which implies differential homing. Here, we show that colonic CD11c(+) APCs imprint CD8(+) T cell preferential homing to the colon, in contrast to those from the small intestine that imprint CD8(+) T cell homing to the small intestine, and that the differences are related to the variable ability of APCs to induce α4β7-integrin and CCR9 expression on T cells...
September 26, 2017: Journal of Leukocyte Biology
Jeremy Kiripolsky, Liam G McCabe, Daniel P Gaile, Jill M Kramer
Sjögren's syndrome (SS) is an autoimmune disease that often results in diminished exocrine gland function. SS patients also experience systemic disease manifestations, including hypergammaglobulinemia and pulmonary and renal pathoses. MyD88 is a ubiquitously expressed adaptor molecule used by all immune cells that is required for IL-1 receptor (IL-1R), IL-18R, and most TLR signaling. The precise role of MyD88 in SS has not been evaluated, although this adaptor is critical for development of lupus, a related autoimmune disease...
September 26, 2017: Journal of Leukocyte Biology
Silvia Lonardi, Sara Licini, Alessandra Micheletti, Giulia Finotti, William Vermi, Marco A Cassatella
The precise identification of the types and respective roles of the tumor-associated myeloid cells, which include tumor-associated Mϕs (TAMs), neutrophils, dendritic cells, and myeloid-derived suppressor cells, is under intensive investigation. Although tumor-associated myeloid cells may contribute to tumor cell eradication by virtue of their effector functions, they are retained to fulfill predominantly protumorigenic roles. It follows that depletion of tumor-associated myeloid cells represents one of the currently pursued therapeutic options in advanced malignancies...
September 26, 2017: Journal of Leukocyte Biology
Jerod A Skyberg, Carolyn A Lacey
Francisella tularensis is a highly infectious intracellular bacterium that causes the potentially fatal disease tularemia. We used mice with conditional MyD88 deficiencies to investigate cellular and molecular mechanisms by which MyD88 restricts type A F. tularensis infection. F. tularensis-induced weight loss was predominately dependent on MyD88 signaling in nonhematopoietic cells. In contrast, MyD88 signaling in hematopoietic cells, but not in myeloid and dendritic cells, was essential for control of F. tularensis infection in tissue...
September 26, 2017: Journal of Leukocyte Biology
Anna Sałkowska, Kaja Karaś, Aurelia Walczak-Drzewiecka, Jarosław Dastych, Marcin Ratajewski
The role of epigenetic mechanisms in the regulation of the human RORγT gene, which encodes a Th17 lymphocyte signature transcription factor, remains largely unknown. We investigated the effect of histone deacetylase (HDAC) inhibition on RORγT and RORγT-dependent gene expression in human T lymphocytes. We found that, in Jurkat T cells and in in vitro-differentiated Th17 cells, treatment with 2 HDAC inhibitors, butyrate and apicidin, led to the induction of the RORγT gene, which was associated with an increase in histone H4 acetylation near the RORγT proximal promoter...
September 26, 2017: Journal of Leukocyte Biology
Catherine Y Cheng, Julia Böhme, Amit Singhal
A wealth of scientific and clinical evidence during the past few years has lent credence to the idea that key components of the host immune effector mechanisms can be targeted to boost current tuberculosis (TB) treatment and control patient relapse. These host-directed strategies not only accelerate the clearance of pathogens but also have the ability to limit overt inflammation and pathology, which are associated with the tissue damage. Studies have indicated that inflammatory responses are intrinsically linked to cellular metabolism and together drive the fate of many host responses, coupling host survival with the capacity to respond to infectious insult...
September 26, 2017: Journal of Leukocyte Biology
Amelia T Soderholm, Timothy C Barnett, Matthew J Sweet, Mark J Walker
Streptococcus pyogenes, the Group A Streptococcus (GAS), is the most common cause of bacterial pharyngitis in children and adults. Innate and adaptive host immune responses are fundamental for defense against streptococcal pharyngitis and are central to the clinical manifestation of disease. Host immune responses also contribute to the severe poststreptococcal immune diseases that constitute the major disease burden for this organism. However, until recently, little was known about the host responses elicited during infection...
September 26, 2017: Journal of Leukocyte Biology
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