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https://www.readbyqxmd.com/read/29669928/cx3cr1-identifies-pd-1-therapy-responsive-cd8-t-cells-that-withstand-chemotherapy-during-cancer-chemoimmunotherapy
#1
Yiyi Yan, Siyu Cao, Xin Liu, Susan M Harrington, Wendy E Bindeman, Alex A Adjei, Jin Sung Jang, Jin Jen, Ying Li, Pritha Chanana, Aaron S Mansfield, Sean S Park, Svetomir N Markovic, Roxana S Dronca, Haidong Dong
Although immune checkpoint inhibitors have resulted in durable clinical benefits in a subset of patients with advanced cancer, some patients who did not respond to initial anti-PD-1 therapy have been found to benefit from the addition of salvage chemotherapy. However, the mechanism responsible for the successful chemoimmunotherapy is not completely understood. Here we show that a subset of circulating CD8+ T cells expressing the chemokine receptor CX3CR1 are able to withstand the toxicity of chemotherapy and are increased in patients with metastatic melanoma who responded to chemoimmunotherapy (paclitaxel and carboplatin plus PD-1 blockade)...
April 19, 2018: JCI Insight
https://www.readbyqxmd.com/read/29669747/the-role-of-the-microglial-cx3cr1-pathway-in-the-post-natal-maturation-of-retinal-photoreceptors
#2
Andrew I Jobling, Michelle Waugh, Kirstan A Vessey, Joanna A Phipps, Lidia Trogrlic, Una Greferath, Samuel A Mills, Zhi L Tan, Michelle M Ward, Erica L Fletcher
Microglia are the resident immune cells of the CNS and their response to infection, injury and disease is well documented. More recently, microglia have been shown to play a role in normal CNS development, with the fractalkine-Cx3cr1 signalling pathway of particular importance. This work describes the interaction between the light sensitive photoreceptors and microglia during eye opening, a time of post-natal photoreceptor maturation. Genetic removal of Cx3cr1 ( Cx3cr1GFP/GFP ), led to an early retinal dysfunction soon after eye opening (P17) and cone photoreceptor loss (P30 onwards) in mice of either sex...
April 18, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29669283/induction-and-maintenance-of-cx3cr1-intermediate-peripheral-memory-cd8-t-cells-by-persistent-viruses-and-vaccines
#3
Claire Louse Gordon, Lian Ni Lee, Leo Swadling, Claire Hutchings, Madeleine Zinser, Andrew John Highton, Stefania Capone, Antonella Folgori, Eleanor Barnes, Paul Klenerman
The induction and maintenance of T cell memory is critical to the success of vaccines. A recently described subset of memory CD8+ T cells defined by intermediate expression of the chemokine receptor CX3CR1 was shown to have self-renewal, proliferative, and tissue-surveillance properties relevant to vaccine-induced memory. We tracked these cells when memory is sustained at high levels: memory inflation induced by cytomegalovirus (CMV) and adenovirus-vectored vaccines. In mice, both CMV and vaccine-induced inflationary T cells showed sustained high levels of CX3R1int cells exhibiting an effector-memory phenotype, characteristic of inflationary pools, in early memory...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29662171/fatal-demyelinating-disease-is-induced-by-monocyte-derived-macrophages-in-the-absence-of-tgf-%C3%AE-signaling
#4
Harald Lund, Melanie Pieber, Roham Parsa, David Grommisch, Ewoud Ewing, Lara Kular, Jinming Han, Keying Zhu, Jik Nijssen, Eva Hedlund, Maria Needhamsen, Sabrina Ruhrmann, André Ortlieb Guerreiro-Cacais, Rasmus Berglund, Maria J Forteza, Daniel F J Ketelhuth, Oleg Butovsky, Maja Jagodic, Xing-Mei Zhang, Robert A Harris
The cytokine transforming growth factor-β (TGF-β) regulates the development and homeostasis of several tissue-resident macrophage populations, including microglia. TGF-β is not critical for microglia survival but is required for the maintenance of the microglia-specific homeostatic gene signature1,2 . Under defined host conditions, circulating monocytes can compete for the microglial niche and give rise to long-lived monocyte-derived macrophages residing in the central nervous system (CNS)3-5 . Whether monocytes require TGF-β for colonization of the microglial niche and maintenance of CNS integrity is unknown...
April 16, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29650776/lymphatic-exosomes-promote-dendritic-cell-migration-along-guidance-cues
#5
Markus Brown, Louise A Johnson, Dario A Leone, Peter Majek, Kari Vaahtomeri, Daniel Senfter, Nora Bukosza, Helga Schachner, Gabriele Asfour, Brigitte Langer, Robert Hauschild, Katja Parapatics, Young-Kwon Hong, Keiryn L Bennett, Renate Kain, Michael Detmar, Michael Sixt, David G Jackson, Dontscho Kerjaschki
Lymphatic endothelial cells (LECs) release extracellular chemokines to guide the migration of dendritic cells. In this study, we report that LECs also release basolateral exosome-rich endothelial vesicles (EEVs) that are secreted in greater numbers in the presence of inflammatory cytokines and accumulate in the perivascular stroma of small lymphatic vessels in human chronic inflammatory diseases. Proteomic analyses of EEV fractions identified >1,700 cargo proteins and revealed a dominant motility-promoting protein signature...
April 12, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29625473/corneal-epithelial-cells-exhibit-myeloid-characteristics-and-present-antigen-via-mhc-class-ii
#6
Derek J Royer, Michael H Elliott, Yun Z Le, Daniel J J Carr
Purpose: To explore the impact of ocular surface insults on the immunomodulatory capacity and phenotype of corneal epithelial cells (CECs) with a focus on epithelial-mesenchymal transition (EMT). Methods: Corneas were harvested from mice 6 days following scratch injury, ragweed pollen-induced allergy, or herpes simplex virus type 1 (HSV-1) infection and compared to healthy tissue controls. Corneas were enzymatically digested and CECs phenotypically characterized using flow cytometry...
March 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29624852/cryopreserved-whole-blood-for-the-quantification-of-monocyte-t-cell-and-nk-cell-subsets-and-monocyte-receptor-expression-by-multi-color-flow-cytometry-a-methodological-study-based-on-participants-from-the-canadian-longitudinal-study-on-aging
#7
Chris P Verschoor, Vikas Kohli
Immunophenotyping by multi-color flow cytometry is arguably the best tool to identify and quantify distinct cell lineages from the peripheral blood and other biological fluids/tissues. Effective in both clinical and research settings, it can be used to estimate the frequency of a given cell type or measure its phenotypic or functional properties. Normally, immunophenotyping is performed in fresh or fractionated blood (i.e., PBMCs) the same day, or within 24 hours of collection; however, this may not be feasible for all study designs...
April 6, 2018: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/29624735/cx3cr1-deficiency-exacerbates-alpha-synuclein-a53t-induced-neuroinflammation-and-neurodegeneration-in-a-mouse-model-of-parkinson-s-disease
#8
Sara Castro-Sánchez, Ángel J García-Yagüe, Tresa López-Royo, Maria Casarejos, José Luis Lanciego, Isabel Lastres-Becker
Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by the degeneration of dopaminergic neurons of the substantia nigra and the accumulation of protein aggregates, called Lewy bodies, where the most abundant is alpha-synuclein (α-SYN). Mutations of the gene that codes for α-SYN (SNCA), such as the A53T mutation, and duplications of the gene generate cases of PD with autosomal dominant inheritance. As a result of the association of inflammation with the neurodegeneration of PD, we analyzed whether overexpression of wild-type α-SYN (α-SYNWT ) or mutated α-SYN (α-SYNA53T ) are involved in the neuronal dopaminergic loss and inflammation process, along with the role of the chemokine fractalkine (CX3CL1) and its receptor (CX3CR1)...
April 6, 2018: Glia
https://www.readbyqxmd.com/read/29568915/aspirin-modulates-the-inflammatory-response-in-a-thrombus%C3%A2-stimulated-lmvec-model
#9
Lingcong Wang, Rongbiao Ying, Huifang Jiang, Qun Jin, Jing Kuang, Zhirong Zhang, Ying Shi, Danli Cai, Ruhui Yang
The purpose of the present study was to examine whether aspirin interferes with the inflammatory response in a thrombus‑stimulated lung microvascular endothelial cell (LMVEC) model. The LMVECs were randomly divided into eight groups: Normal group (group N), model group (group M), model + ASP group (group M+A), model+CX3CL1‑short hairpin (sh)RNA group (group M+SH), model + CX3CL1‑overexpression vector group (group M+CX3), model + ASP + shRNA group (group M+A+SH), model + ASP + CX3CL1‑overexpression vector group (group M+A+CX3), and normal + virus control group (group N+V)...
March 13, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29568873/the-deficiency-of-cx3cl1-cx3cr1-system-ameliorates-high-fructose-diet-induced-kidney-injury-by-regulating-nf-%C3%AE%C2%BAb-pathways-in-cx3cr1-knock-out-mice
#10
Yong-Wu Yu, Ming-Xu Li, Zhi-Yong Zhang, Hai Yu
Fructose, the most important functional food additive from the last century, has been widely used in industry, agriculture, light industry, food and medicine. With the improvement of people's living standard and economic level, excess intake of fructose results in metabolic symptoms, including hyperleptinemia, insulin resistance and neuroinflammation is causing high risk of chronic kidney disease development in humans and animals. However, the underlying molecular mechanism of renal injury is still not fully understood, and the development of effective drugs and treatments are delayed...
June 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29565837/polymorphisms-in-selected-genes-and-their-association-with-age-related-macular-degeneration-in-a-chinese-population
#11
Qing Huang, Yi Xiang
BACKGROUND Increasing evidence shows that polymorphisms in a number of genes can influence age-related macular degeneration (AMD) risk. This study aimed to investigate the association of CX3CR1 839C/T, CX3CR1 745G/A, PLEKHA1 958A/G, VEGFA +674C/T, and VEGFA +936C/T polymorphisms with AMD risk among Chinese. MATERIAL AND METHODS The polymorphisms were genotyped on 827 AMD patients and 827 controls, and the odds ratios (ORs) were calculated under allele, additive, recessive, and dominant genetic models. Logistic regression analysis was performed to control for potential confounders (age, sex, and smoking status)...
March 22, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29548673/sensing-microbial-viability-through-bacterial-rna-augments-t-follicular-helper-cell-and-antibody-responses
#12
Gaetan Barbet, Leif E Sander, Matthew Geswell, Irina Leonardi, Andrea Cerutti, Iliyan Iliev, J Magarian Blander
Live vaccines historically afford superior protection, yet the cellular and molecular mechanisms mediating protective immunity remain unclear. Here we found that vaccination of mice with live, but not dead, Gram-negative bacteria heightened follicular T helper cell (Tfh) differentiation, germinal center formation, and protective antibody production through the signaling adaptor TRIF. Complementing the dead vaccine with an innate signature of bacterial viability, bacterial RNA, recapitulated these responses...
March 20, 2018: Immunity
https://www.readbyqxmd.com/read/29545116/role-of-the-chemokine-receptors-ccr2-and-cx3cr1-in-an-experimental-model-of-thrombotic-stroke
#13
Giulia Cisbani, Audrey Le Behot, Marie-Michèle Plante, Paul Préfontaine, Manon Lecordier, Serge Rivest
Stroke is the second cause of mortality worldwide and occurs following the interruption of cerebral blood circulation by cerebral vessel burst or subsequent to a local thrombus formation. Ischemic lesion triggers an important inflammatory response, characterized by massive infiltration of leukocytes, activation of glial cells and neurovascular reorganization. Chemokines and their receptors, such as CCR2 and CX3CR1, play an important role in leukocyte recruitment in the damaged area. Mice genetically depleted for the two receptors CCR2 and CX3CR1 underwent focal cerebral ischemia, based on the topical application of ferric chloride to truncate the distal middle cerebral artery...
March 12, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29523582/structures-of-respiratory-syncytial-virus-g-antigen-bound-to-broadly-neutralizing-antibodies
#14
Stanislav O Fedechkin, Natasha L George, Jacob T Wolff, Lawrence M Kauvar, Rebecca M DuBois
Respiratory syncytial virus (RSV) is a top cause of severe lower respiratory tract disease and mortality in young children and the elderly. The viral envelope G glycoprotein contributes to pathogenesis through its roles in host cell attachment and modulation of host immunity. Although the G glycoprotein is a target of protective RSV-neutralizing antibodies, its development as a vaccine antigen has been hindered by its heterogeneous glycosylation and sequence variability outside a conserved central domain (CCD)...
March 9, 2018: Science Immunology
https://www.readbyqxmd.com/read/29509814/structural-basis-for-recognition-of-the-central-conserved-region-of-rsv-g-by-neutralizing-human-antibodies
#15
Harrison G Jones, Tina Ritschel, Gabriel Pascual, Just P J Brakenhoff, Elissa Keogh, Polina Furmanova-Hollenstein, Ellen Lanckacker, Jehangir S Wadia, Morgan S A Gilman, R Anthony Williamson, Dirk Roymans, Angélique B van 't Wout, Johannes P Langedijk, Jason S McLellan
Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections in infants and the elderly, and yet there remains no effective treatment or vaccine. The surface of the virion is decorated with the fusion glycoprotein (RSV F) and the attachment glycoprotein (RSV G), which binds to CX3CR1 on human airway epithelial cells to mediate viral attachment and subsequent infection. RSV G is a major target of the humoral immune response, and antibodies that target the central conserved region of G have been shown to neutralize both subtypes of RSV and to protect against severe RSV disease in animal models...
March 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29505094/phenotypic-and-functional-heterogeneity-of-human-intermediate-monocytes-based-on-hla-dr-expression
#16
Eanna P Connaughton, Serika Naicker, Shirley A Hanley, Stephanie M Slevin, John K Eykelenboom, Noel F Lowndes, Timothy O'Brien, Rhodri Ceredig, Matthew D Griffin, Michael C Dennedy
Human blood monocytes are sub-classified as classical, intermediate and non-classical. In this study, it was shown that conventionally-defined human intermediate monocytes (IM) can be divided into two distinct subpopulations with mid- and high-level surface expression of HLA-DR (referred to as DRmid and DRhi IM). These IM subpopulations were phenotypically and functionally characterized in healthy adult blood by flow cytometry, migration assays and lipoprotein uptake assays. Their absolute numbers and proportions were then compared in blood samples from obese and non-obese adults...
March 5, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29504946/chronic-fractalkine-administration-improves-glucose-tolerance-and-pancreatic-endocrine-function
#17
Matthew Riopel, Jong Bae Seo, Gautam K Bandyopadhyay, Pingping Li, Joshua Wollam, Heekyung Chung, Seung-Ryoung Jung, Anne Murphy, Maria Wilson, Ron de Jong, Sanjay Patel, Deepika Balakrishna, James Bilakovics, Andrea Fanjul, Artur Plonowski, Duk-Su Koh, Christopher J Larson, Jerrold M Olefsky, Yun Sok Lee
We have previously reported that the fractalkine (FKN)/CX3CR1 system represents a novel regulatory mechanism for insulin secretion and β cell function. Here, we demonstrate that chronic administration of a long-acting form of FKN, FKN-Fc, can exert durable effects to improve glucose tolerance with increased glucose-stimulated insulin secretion and decreased β cell apoptosis in obese rodent models. Unexpectedly, chronic FKN-Fc administration also led to decreased α cell glucagon secretion. In islet cells, FKN inhibited ATP-sensitive potassium channel conductance by an ERK-dependent mechanism, which triggered β cell action potential (AP) firing and decreased α cell AP amplitude...
March 5, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29487809/monocyte-chemoattractant-protein-1-and-fractalkine-play-opposite-roles-in-angiogenesis-via-recruitment-of-different-macrophage-subtypes
#18
Lei Chen, Gao-Qin Liu, Hong-Ya Wu, Ji Jin, Xue Yin, Dan Li, Pei-Rong Lu
AIM: To explore the interaction between macrophages and chemokines [monocyte chemoattractant protein 1 (MCP-1/CCL2) and fractalkine/CX3CL1] and the effects of their interaction on neovascularization. METHODS: Human peripheral blood mononuclear cells, donated by healthy volunteers, were separated and cultured in RPMI-1640 medium containing 10% fetal bovine serum, then induced into macrophages by stimulation with 30 µg/L granulocyte macrophage-colony stimulating factor (GM-CSF)...
2018: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/29485193/polymorphisms-in-the-microglial-marker-molecule-cx3cr1-affect-the-blood-volume-of-the-human-brain
#19
Mai Sakai, Hikaru Takeuchi, Zhiqian Yu, Yoshie Kikuchi, Chiaki Ono, Yuta Takahashi, Fumiaki Ito, Hiroo Matsuoka, Osamu Tanabe, Jun Yasuda, Yasuyuki Taki, Ryuta Kawashima, Hiroaki Tomita
AIMS: CX3CR1, a G-protein-coupled receptor, is involved in various inflammatory processes. Two non-synonymous single nucleotide polymorphisms, V249I (rs3732379) and T280M (rs3732378), are located in the sixth and seventh transmembrane domains of the CX3CR1 protein, respectively. Previous studies indicated significant associations between T280M and leukocyte functional characteristics, including adhesion, signaling, and chemotaxis, while the function of V249I is unclear. In the brain, microglia are the only proven and widely accepted CX3CR1-expressing cells...
February 27, 2018: Psychiatry and Clinical Neurosciences
https://www.readbyqxmd.com/read/29465317/neuroprotective-effects-of-silibinin-an-in-silico-and-in-vitro-study
#20
Valencia Fernandes, Dilip Sharma, Kiran Kalia, Vinod Tiwari
Astrogliosis is a key contributor for many neurological disorders involving apoptosis, neuroinflammation and subsequent neuronal death. Silibinin, a polyphenol isolated from milk thistle (Silybum marianum), has been shown to suppress the astrocyte activation in various neurodegenerative disorders and also exhibit a neuroprotective role in neuroinflammation-driven oxidative damage. In the present study, we found that treatment with silibinin significantly attenuates LPS- oxidative-nitrosative stress in C6 astrocytoma cells...
February 21, 2018: International Journal of Neuroscience
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