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https://www.readbyqxmd.com/read/28810923/the-chemokine-fractalkine-cx3cl1-attenuates-h2o2-induced-demyelination-in-cerebellar-slices
#1
Sinead A O'Sullivan, Kumlesh K Dev
BACKGROUND: Fractalkine/CX3CR1 signalling has been implicated in many neurodegenerative and neurological diseases of the central nervous system (CNS). This signalling pathway plays an important role in regulating reactive oxygen species (ROS), as well as itself being altered in conditions of oxidative stress. Here, we investigated the effects of recombinant fractalkine (rCX3CL1) in models of hydrogen peroxide (H2O2)-induced demyelination and astrocyte toxicity, within organotypic cerebellar slice cultures...
August 15, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28810892/absence-of-cx3cr1-impairs-the-internalization-of-tau-by-microglia
#2
Marta Bolós, María Llorens-Martín, Juan Ramón Perea, Jerónimo Jurado-Arjona, Alberto Rábano, Félix Hernández, Jesús Avila
BACKGROUND: Extracellular Tau is toxic for neighboring cells, and it contributes to the progression of AD. The CX3CL1/CX3CR1 axis is an important neuron/microglia communication mechanism. METHODS: We studied Tau clearance by microglia both in vitro (microglia primary cultures treated with Cy5-Tau, affinity chromatography to study the binding of Tau to CX3CR1, and Tau-CX3CL1 competition assays) and in vivo (stereotaxic injection of Cy5-Tau into WT and CX3CR1(-/-) mice)...
August 15, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28801233/t-cell-zone-resident-macrophages-silently-dispose-of-apoptotic-cells-in-the-lymph-node
#3
Myriam Baratin, Léa Simon, Audrey Jorquera, Clément Ghigo, Doulaye Dembele, Jonathan Nowak, Rebecca Gentek, Stephan Wienert, Frederick Klauschen, Bernard Malissen, Marc Dalod, Marc Bajénoff
In lymph nodes (LNs), dendritic cells (DCs) are thought to dispose of apoptotic cells, a function pertaining to macrophages in other tissues. We found that a population of CX3CR1(+) MERTK(+) cells located in the T cell zone of LNs, previously identified as DCs, are efferocytic macrophages. Lineage-tracing experiments and shield chimeras indicated that these T zone macrophages (TZM) are long-lived macrophages seeded in utero and slowly replaced by blood monocytes after birth. Imaging the LNs of mice in which TZM and DCs express different fluorescent proteins revealed that TZM-and not DCs-act as the only professional scavengers, clearing apoptotic cells in the LN T cell zone in a CX3CR1-dependent manner...
August 15, 2017: Immunity
https://www.readbyqxmd.com/read/28800592/cx3cr1-knockout-aggravates-coxsackievirus-b3-induced-myocarditis
#4
Irene Müller, Kathleen Pappritz, Konstantinos Savvatis, Kerstin Puhl, Fengquan Dong, Muhammad El-Shafeey, Nazha Hamdani, Isabell Hamann, Michel Noutsias, Carmen Infante-Duarte, Wolfgang A Linke, Sophie Van Linthout, Carsten Tschöpe
Studies on inflammatory disorders elucidated the pivotal role of the CX3CL1/CX3CR1 axis with respect to the pathophysiology and diseases progression. Coxsackievirus B3 (CVB3)-induced myocarditis is associated with severe cardiac inflammation, which may progress to heart failure. We therefore investigated the influence of CX3CR1 ablation in the model of acute myocarditis, which was induced by inoculation with 5x105 plaque forming units of CVB3 (Nancy strain) in either CX3CR1-/- or C57BL6/j (WT) mice. Seven days after infection, myocardial inflammation, remodeling, and titin expression and phosphorylation were examined by immunohistochemistry, real-time PCR and Pro-Q diamond stain...
2017: PloS One
https://www.readbyqxmd.com/read/28793053/cerebrospinal-fluid-contacting-nucleus-mediates-nociception-via-release-of-fractalkine
#5
Q Q Zhou, S S Chen, Q Q Zhang, P F Liu, H Z Fang, Y Yang, L C Zhang
Increasing evidence suggests that the cerebrospinal fluid-contacting nucleus (CSF-contacting nucleus) mediates the transduction and regulation of pain signals. However, the precise molecular mechanisms remain unclear. Studies show that release of fractalkine (FKN) from neurons plays a critical role in nerve injury-related pain. We tested the hypothesis that release of FKN from the CSF-contacting nucleus regulates neuropathic pain, in a chronic constriction injury rat model. The results show that FKN is expressed by neurons, via expression of its only receptor CX3CR1 in the microglia...
August 7, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28791023/tgf-%C3%AE-1-downregulates-the-expression-of-cx3cr1-by-inducing-mir-27a-5p-in-primary-human-nk-cells
#6
Stefano Regis, Fabio Caliendo, Alessandra Dondero, Beatrice Casu, Filomena Romano, Fabrizio Loiacono, Alessandro Moretta, Cristina Bottino, Roberta Castriconi
Activity of human natural killer (NK) cells against cancer cells is deeply suppressed by TGF-β1, an immunomodulatory cytokine that is released and activated in the tumor microenvironment. Moreover, our previous data showed that TGF-β1 modifies the chemokine receptor repertoire of NK cells. In particular, it decreases the expression of CX3CR1 that drives these effectors toward peripheral tissues, including tumor sites. To identify possible mechanisms mediating chemokine receptors modulation, we analyzed the microRNA profile of TGF-β1-treated primary NK cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28776289/spinal-cx3cl1-cx3cr1-may-not-directly-participate-in-the-development-of-morphine-tolerance-in-rats
#7
Yawen Peng, Genhua Guo, Bin Shu, Daiqiang Liu, Peng Su, Xuming Zhang, Feng Gao
CX3CL1 (fractalkine), the sole member of chemokine CX3C family, is implicated in inflammatory and neuropathic pain via activating its receptor CX3CR1 on neural cells in spinal cord. However, it has not been fully elucidated whether CX3CL1 or CX3CR1 contributes to the development of morphine tolerance. In this study, we found that chronic morphine exposure did not alter the expressions of CX3CL1 and CX3CR1 in spinal cord. And neither exogenous CX3CL1 nor CX3CR1 inhibitor could affect the development of morphine tolerance...
August 3, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28769122/modulation-of-gr1-low-monocytes-subset-impacts-insulin-sensitivity-and-weight-gain-upon-high-fat-diet-in-female-mice
#8
S Béliard, W Le Goff, F Saint-Charles, L Poupel, V Deaswerte, L Boucharechas, T Huby, P Lesnik
BACKGROUND/OBJECTIVES: Blood monocytes are expanded during obesity. However, the differential contribution of monocytes subsets in obesity-related metabolic disorders remains unknown. The aim of the study was to define the role of the Gr1(low) monocytes subset upon high-fat-diet (HFD). METHODS: We used transgenic female mouse models allowing the modulation of circulating Gr1(low) monocytes number (decreased number in CX3CR1(-/-) mice, increased number in CD11c-hBcl2 mice) and studied obesity upon HFD...
August 3, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28768911/a-ccr2-myeloid-cell-niche-required-for-pancreatic-%C3%AE-cell-growth
#9
Kristin Mussar, Stephanie Pardike, Tobias M Hohl, Gary Hardiman, Vincenzo Cirulli, Laura Crisa
Organ-specific patterns of myeloid cells may contribute tissue-specific growth and/or regenerative potentials. The perinatal stage of pancreas development marks a time characterized by maximal proliferation of pancreatic islets, ensuring the maintenance of glucose homeostasis throughout life. Ontogenically distinct CX3CR1+ and CCR2+ macrophage populations have been reported in the adult pancreas, but their functional contribution to islet cell growth at birth remains unknown. Here, we uncovered a temporally restricted requirement for CCR2+ myeloid cells in the perinatal proliferation of the endocrine pancreatic epithelium...
August 3, 2017: JCI Insight
https://www.readbyqxmd.com/read/28763796/the-metabolic-regulator-mtorc1-controls-terminal-myeloid-differentiation
#10
Pui Y Lee, David B Sykes, Sarah Ameri, Demetrios Kalaitzidis, Julia F Charles, Nathan Nelson-Maney, Kevin Wei, Pierre Cunin, Allyn Morris, Astrid E Cardona, David E Root, David T Scadden, Peter A Nigrovic
Monocytes are derived from hematopoietic stem cells through a series of intermediate progenitor stages, but the factors that regulate this process are incompletely defined. Using a Ccr2/Cx3cr1 dual-reporter system to model murine monocyte ontogeny, we conducted a small-molecule screen that identified an essential role of mechanistic target of rapamycin complex 1 (mTORC1) in the development of monocytes and other myeloid cells. Confirmatory studies using mice with inducible deletion of the mTORC1 component Raptor demonstrated absence of mature circulating monocytes, as well as disruption in neutrophil and dendritic cell development, reflecting arrest of terminal differentiation at the granulocyte-monocyte progenitor stage...
May 26, 2017: Science Immunology
https://www.readbyqxmd.com/read/28763059/rare-genetic-variants-in-cx3cr1-and-their-contribution-to-the-increased-risk-of-schizophrenia-and-autism-spectrum-disorders
#11
K Ishizuka, Y Fujita, T Kawabata, H Kimura, Y Iwayama, T Inada, Y Okahisa, J Egawa, M Usami, I Kushima, Y Uno, T Okada, M Ikeda, B Aleksic, D Mori, To Someya, T Yoshikawa, N Iwata, H Nakamura, T Yamashita, N Ozaki
CX3CR1, a G protein-coupled receptor solely expressed by microglia in the brain, has been repeatedly reported to be associated with neurodevelopmental disorders including schizophrenia (SCZ) and autism spectrum disorders (ASD) in transcriptomic and animal studies but not in genetic studies. To address the impacts of variants in CX3CR1 on neurodevelopmental disorders, we conducted coding exon-targeted resequencing of CX3CR1 in 370 Japanese SCZ and 192 ASD patients using next-generation sequencing technology, followed by a genetic association study in a sample comprising 7054 unrelated individuals (2653 SCZ, 574 ASD and 3827 controls)...
August 1, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28754163/choroid-plexus-cerebrospinal-fluid-route-for-monocyte-derived-macrophages-after-stroke
#12
Ruimin Ge, Daniel Tornero, Masao Hirota, Emanuela Monni, Cecilia Laterza, Olle Lindvall, Zaal Kokaia
BACKGROUND: Choroid plexus (CP) supports the entry of monocyte-derived macrophages (MDMs) to the central nervous system in animal models of traumatic brain injury, spinal cord injury, and Alzheimer's disease. Whether the CP is involved in the recruitment of MDMs to the injured brain after ischemic stroke is unknown. METHODS: Adult male C57BL/6 mice were subjected to focal cortical ischemia by permanent occlusion of the distal branch of the right middle cerebral artery...
July 28, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28747747/involvement-of-monocyte-subsets-in-the-immunopathology-of-giant-cell-arteritis
#13
Yannick van Sleen, Qi Wang, Kornelis S M van der Geest, Johanna Westra, Wayel H Abdulahad, Peter Heeringa, Annemieke M H Boots, Elisabeth Brouwer
Monocytes/macrophages are critical in systemic and local inflammation in giant cell arteritis (GCA) and possibly in clinically overlapping polymyalgia rheumatica (PMR). Therefore, we aimed to understand the contribution of monocyte subsets and the CX3CR1-CX3CL1 and CCR2-CCL2 migratory pathways, to the pathology of GCA. Peripheral blood monocytes were enumerated in samples from newly-diagnosed, untreated GCA and PMR patients and after prednisone-induced remission. The distribution of classical (CD14(bright)CD16(neg)) and the more pro-inflammatory, intermediate (CD14(bright)CD16+) and non-classical (CD14(dim)CD16+) monocyte subsets was analysed by flow cytometry...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28745326/defective-positioning-in-granulomas-but-not-lung-homing-limits-cd4-t-cell-interactions-with-mycobacterium-tuberculosis-infected-macrophages-in-rhesus-macaques
#14
K D Kauffman, M A Sallin, S Sakai, O Kamenyeva, J Kabat, D Weiner, M Sutphin, D Schimel, L Via, C E Barry, T Wilder-Kofie, I Moore, R Moore, D L Barber
Protection against Mycobacterium tuberculosis (Mtb) infection requires CD4 T cells to migrate into the lung and interact with infected macrophages. In mice, less-differentiated CXCR3(+) CD4 T cells migrate into the lung and suppress growth of Mtb, whereas CX3CR1(+) terminally differentiated Th1 cells accumulate in the blood vasculature and do not control pulmonary infection. Here we examine CD4 T-cell differentiation and lung homing during primary Mtb infection of rhesus macaques. Mtb-specific CD4 T cells simultaneously appeared in the airways and blood ∼21-28 days post exposure, indicating that recently primed effectors are quickly recruited into the lungs after entering circulation...
July 26, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28736330/impaired-microglia-fractalkine-signaling-affects-stress-reaction-and-coping-style-in-mice
#15
Zsuzsanna Winkler, Dániel Kuti, Szilamér Ferenczi, Krisztina Gulyás, Ágnes Polyák, Krisztina J Kovács
Microglia, resident immune cells of the CNS are sensitive to various perturbations of the environment, such as stress exposure, and may be involved in translating these changes to behavior. Among the pathways mediating stress-related neuronal cues to microglia, the fractalkine-fractalkine receptor (CX3CR1) signaling plays a crucial role. Using mice, in which the CX3CR1 gene was deleted, we explored hormonal and behavioral responses to acute and chronic stress along with changes in hypothalamic microglia. CX3CR1(-/-) animals display active escape in forced swim- and tail suspension tests, exaggerated neuronal activation in the hypothalamic paraventricular nucleus and increased corticosterone release in response to restraint...
July 20, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28727998/enrichment-of-endogenous-fractalkine-and-anti-inflammatory-cells-via-aptamer-functionalized-hydrogels
#16
Syed Faaiz Enam, Jack R Krieger, Tarun Saxena, Brian E Watts, Claire E Olingy, Edward A Botchwey, Ravi V Bellamkonda
Early recruitment of non-classical monocytes and their macrophage derivatives is associated with augmented tissue repair and improved integration of biomaterial constructs. A promising therapeutic approach to recruit these subpopulations is by elevating local concentrations of chemoattractants such as fractalkine (FKN, CX3CL1). However, delivering recombinant or purified proteins is not ideal due to their short half-lives, suboptimal efficacy, immunogenic potential, batch variabilities, and cost. Here we report an approach to enrich endogenous FKN, obviating the need for delivery of exogenous proteins...
October 2017: Biomaterials
https://www.readbyqxmd.com/read/28723545/spineless-behavior-of-cx3cr1-monocytes-in-response-to-infection
#17
Paul A Muller, Daniel Mucida
Sickness in mammals can lead to cognition deficits, although the underlying mechanisms remain elusive. In a recent Nature Medicine article, Garré et al. (2017) report that sickness-induced cortical dendritic spine loss and impaired memory formation is mediated by CX3CR1(+) monocyte-derived TNF-α.
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28717419/platelet-extracellular-vesicles-induce-a-pro-inflammatory-smooth-muscle-cell-phenotype
#18
Tanja Vajen, Birke J Benedikter, Alexandra C A Heinzmann, Elena M Vasina, Yvonne Henskens, Martin Parsons, Patricia B Maguire, Frank R Stassen, Johan W M Heemskerk, Leon J Schurgers, Rory R Koenen
Extracellular vesicles (EVs) are mediators of cell communication during health and disease, and abundantly released by platelets upon activation or during ageing. Platelet EVs exert modulatory effects on immune and vascular cells. Platelet EVs may modulate the function of vascular smooth muscle cells (SMC). Platelet EVs were isolated from platelet-rich plasma and incubated with SMC in order to assess binding, proliferation, migration and pro-inflammatory phenotype of the cells. Platelet EVs firmly bound to resting SMC through the platelet integrin αIIbβ3, while binding also occurred in a CX3CL1-CX3CR1-dependent manner after cytokine stimulation...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28716963/chemokine-ccl2-ccr2-signaling-induces-neuronal-cell-death-via-stat3-activation-and-il-1%C3%AE-production-after-status-epilepticus
#19
Dai-Shi Tian, Jiyun Peng, Madhuvika Murugan, Lijie Feng, Jun-Li Liu, Ukpong B Eyo, Li-Jun Zhou, Rochelle Mogilevsky, Wei Wang, Long-Jun Wu
Elevated levels of chemokine C-C motif ligand 2 (CCL2) and its receptor CCR2 have been reported in patients with temporal lobe epilepsy and in experimental seizures. However, the functional significance and molecular mechanism underlying CCL2-CCR2 signaling in epileptic brain remains largely unknown. In this study, we found that the upregulated CCL2 was mainly expressed in hippocampal neurons and activated microglia from mice 1d after kainic acid (KA)-induced seizures. Taking advantage of CX3CR1(GFP/+):CCR2(RFP/+) double transgenic mice, we demonstrated that CCL2-CCR2 signaling participated in resident microglial activation and blood-derived monocyte infiltration...
July 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28696300/acetylcholine-producing-nk-cells-attenuate-cns-inflammation-via-modulation-of-infiltrating-monocytes-macrophages
#20
Wei Jiang, Daojing Li, Ranran Han, Chao Zhang, Wei-Na Jin, Kristofer Wood, Qiang Liu, Fu-Dong Shi, Junwei Hao
The nonneural cholinergic system of immune cells is pivotal for the maintenance of immunological homeostasis. Here we demonstrate the expression of choline acetyltransferase (ChAT) and cholinergic enzymes in murine natural killer (NK) cells. The capacity for acetylcholine synthesis by NK cells increased markedly under inflammatory conditions such as experimental autoimmune encephalomyelitis (EAE), in which ChAT expression escalated along with the maturation of NK cells. ChAT(+) and ChAT(-) NK cells displayed distinctive features in terms of cytotoxicity and chemokine/cytokine production...
July 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
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