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https://www.readbyqxmd.com/read/28101527/regulation-of-physical-microglia-neuron-interactions-by-fractalkine-signaling-after-status-epilepticus
#1
Ukpong B Eyo, Jiyun Peng, Madhuvika Murugan, Mingshu Mo, Almin Lalani, Ping Xie, Pingyi Xu, David J Margolis, Long-Jun Wu
Microglia, the resident immune cells of the brain, perform elaborate surveillance in which they physically interact with neuronal elements. A novel form of microglia-neuron interaction named microglial process convergence (MPC) toward neuronal axons and dendrites has recently been described. However, the molecular regulators and pathological relevance of MPC have not been explored. Here, using high-resolution two-photon imaging in vivo and ex vivo, we observed a dramatic increase in MPCs after kainic acid- or pilocarpine-induced experimental seizures that was reconstituted after glutamate treatment in slices from mice...
November 2016: ENeuro
https://www.readbyqxmd.com/read/28092668/upregulation-of-ret-induces-perineurial-invasion-of-pancreatic-adenocarcinoma
#2
M Amit, S Na'ara, L Leider-Trejo, Y Binenbaum, N Kulish, E Fridman, A Shabtai-Orbach, R J Wong, Z Gil
Tumor spread along nerves, a phenomenon known as perineurial invasion, is common in various cancers including pancreatic ductal adenocarcinoma (PDAC). Neural invasion is associated with poor outcome, yet its mechanism remains unclear. Using the transgenic Pdx-1-Cre/KrasG12D /p53R172H (KPC) mouse model, we investigated the mechanism of neural invasion in PDAC. To detect tissue-specific factors that influence neural invasion by cancer cells, we characterized the perineurial microenvironment using a series of bone marrow transplantation (BMT) experiments in transgenic mice expressing single mutations in the Cx3cr1, GDNF and CCR2 genes...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28088249/interactions-of-human-microglia-cells-with-japanese-encephalitis-virus
#3
Nils Lannes, Viviane Neuhaus, Brigitte Scolari, Solange Kharoubi-Hess, Michael Walch, Artur Summerfield, Luis Filgueira
BACKGROUND: Japanese encephalitis virus (JEV) is a neurotropic flavivirus causing mortality and morbidity in humans. Severe Japanese encephalitis cases display strong inflammatory responses in the central nervous system and an accumulation of viral particles in specific brain regions. Microglia cells are the unique brain-resident immune cell population with potent migratory functions and have been proposed to act as a viral reservoir for JEV. Animal models suggest that the targeting of microglia by JEV is partially responsible for inflammatory reactions in the brain...
January 14, 2017: Virology Journal
https://www.readbyqxmd.com/read/28069536/m2-macrophages-infusion-ameliorates-obesity-and-insulin-resistance-by-remodeling-inflammatory-macrophages-homeostasis-in-obese-mice
#4
Qi Zhang, Haojie Hao, Zongyan Xie, Yu Cheng, Yaqi Yin, Min Xie, Hong Huang, Jieqing Gao, Hongyu Liu, Chuan Tong, Li Zang, Yiming Mu, Weidong Han
OBJECTIVE: The role of M2 macrophages infusion in dealing with obesity is still little known. In this study, the therapeutic effects of M2 macrophages infusion were investigated. METHODS: High fat diet (HFD) was used to induce obesity in C57BL/6N mice. 5 × 10(5) M2 macrophages, derived from the bone marrow, were injected into obese mice through the tail vein twice with an interval of one week. RESULTS: One week after the second injection, weight of inguinal adipose pad was significantly decreased...
January 6, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28066794/altered-monocyte-and-endothelial-cell-adhesion-molecule-expression-is-linked-to-vascular-inflammation-in-human-immunodeficiency-virus-infection
#5
Manjusha Kulkarni, Emily Bowman, Janelle Gabriel, Taylor Amburgy, Elizabeth Mayne, David A Zidar, Courtney Maierhofer, Abigail Norris Turner, Jose A Bazan, Susan L Koletar, Michael M Lederman, Scott F Sieg, Nicholas T Funderburg
BACKGROUND: Human immunodeficiency virus (HIV)-infected individuals have increased risk for vascular thrombosis, potentially driven by interactions between activated leukocytes and the endothelium. METHODS: Monocyte subsets (CD14(+)CD16(-), CD14(+)CD16(+), CD14(Dim)CD16(+)) from HIV negative (HIV(-)) and antiretroviral therapy-treated HIV positive (HIV(+)) participants (N = 19 and 49) were analyzed by flow cytometry for adhesion molecule expression (lymphocyte function-associated antigen 1 [LFA-1], macrophage-1 antigen [Mac-1], CD11c/CD18, very late antigen [VLA]-4) and the fractalkine receptor (CX3CR1); these receptors recognize ligands (intercellular adhesion molecules [ICAMs], vascular cell adhesion molecule [VCAM]-1, fractalkine) on activated endothelial cells (ECs) and promote vascular migration...
October 2016: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28061814/cx3c-chemokine-receptor-1-deficiency-modulates-microglia-morphology-but-does-not-affect-lesion-size-and-short-term-deficits-after-experimental-stroke
#6
Gerlinde van der Maten, Vivien Henck, Tadeusz Wieloch, Karsten Ruscher
BACKGROUND: The fractalkine/CX3C chemokine receptor 1 (CX3CR1) pathway has been identified to play an essential role in the chemotaxis of microglia, leukocyte trafficking and microglia/macrophage recruitment. It has also been shown to be important in the regulation of the inflammatory response in the early phase after experimental stroke. The present study was performed to investigate if CX3CR1 deficiency affects microglia during the first 14 days with consequences for tissue damage after experimental stroke...
January 6, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28044051/maturation-phenotype-of-peripheral-blood-monocyte-macrophage-after-stimulation-with-lipopolysaccharides-in-irritable-bowel-syndrome
#7
Oscar A Rodríguez-Fandiño, Joselín Hernández-Ruiz, Yolanda López-Vidal, Luis Charúa-Guindic, Galileo Escobedo, Max J Schmulson
Background/Aims: Abnormal immune regulation and increased intestinal permeability augmenting the passage of bacterial molecules that can activate immune cells, such as monocytes/macrophages, have been reported in irritable bowel syndrome (IBS). To compare the maturation phenotype of monocytes/macrophages (CD14+) from IBS patients and controls in the presence or absence of E. coli lipopolysaccharides (LPS), in vitro. Methods: Mononuclear cells were isolated from peripheral blood of 20 Rome II-IBS patients and 19 controls and cultured with or without LPS for 72 hours...
January 2, 2017: Journal of Neurogastroenterology and Motility
https://www.readbyqxmd.com/read/28031342/transcriptional-classification-and-functional-characterization-of-human-airway-macrophage-and-dendritic-cell-subsets
#8
Vineet I Patel, J Leland Booth, Elizabeth S Duggan, Steven Cate, Vicky L White, David Hutchings, Susan Kovats, Dennis M Burian, Mikhail Dozmorov, Jordan P Metcalf
The respiratory system is a complex network of many cell types, including subsets of macrophages and dendritic cells that work together to maintain steady-state respiration. Owing to limitations in acquiring cells from healthy human lung, these subsets remain poorly characterized transcriptionally and phenotypically. We set out to systematically identify these subsets in human airways by developing a schema of isolating large numbers of cells by whole-lung bronchoalveolar lavage. Six subsets of phagocytic APC (HLA-DR(+)) were consistently observed...
December 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28028627/effect-of-electroacupuncture-on-the-cervicospinal-p2x7-receptor-fractalkine-cx3cr1-signaling-pathway-in-a-rat-neck-incision-pain-model
#9
Y H Gao, C W Li, J Y Wang, L H Tan, C L Duanmu, X H Jing, X R Chang, J L Liu
Increasing evidence supports that acupuncture intervention is an effective approach for intraoperative and postoperative pain. Neuron-microglia crosstalk, mediated by the purinergic P2X7 receptor (R)/fractalkine/CX3CR1 cascade in the spinal cord dorsal horn, plays a pivotal role in pain processing. However, its involvement in the analgesic effect of electroacupuncture (EA) remains unclear. In this study, a rat neck-incision pain model was established by making a longitudinal incision along the midline of the neck and subsequent repeated mechanical stimulation...
December 27, 2016: Purinergic Signalling
https://www.readbyqxmd.com/read/28026094/phenotypic-characteristics-of-aged-cd4-cd28-null-t-lymphocytes-are-determined-by-changes-in-the-whole-genome-dna-methylation-pattern
#10
Beatriz Suarez-Álvarez, Ramón M Rodríguez, Karin Schlangen, Aroa Baragaño Raneros, Leonardo Márquez-Kisinousky, Agustín F Fernández, Carmen Díaz-Corte, Ana M Aransay, Carlos López-Larrea
Aging is associated with a progressive loss of the CD28 costimulatory molecule in CD4(+) lymphocytes (CD28(null) T cells), which is accompanied by the acquisition of new biological and functional properties that give rise to an impaired immune response. The regulatory mechanisms that govern the appearance and function of this cell subset during aging and in several associated inflammatory disorders remain controversial. Here, we present the whole-genome DNA methylation and gene expression profiles of CD28(null) T cells and its CD28(+) counterpart...
December 27, 2016: Aging Cell
https://www.readbyqxmd.com/read/28011675/cx3cr1-dependent-endothelial-margination-modulates-ly6chigh-monocyte-systemic-deployment-upon-inflammation-in-mice
#11
Pauline Hamon, Pierre-Louis Loyher, Camille Baudesson de Chanville, Fabrice Licata, Christophe Combadière, Alexandre Boissonnas
Two subsets of blood monocytes are commonly described in mice and humans; the classical inflammatory monocytes which are rapidly mobilized upon inflammation in a CC-chemokine receptor 2 (CCR2)-dependent manner, and the non-classical blood resident monocyte subset that patrol the intraluminal side of the endothelium. Old reports suggest that blood monocytes are distributed into circulating and marginating pools but no direct evidence of the latter has been obtained so far. Using a combination of in vivo real-time imaging and blood/tissue partitioning by intravascular staining of leukocytes, we showed that both inflammatory and resident monocytes are retained in the bone marrow vasculature, representing an important reservoir of marginated monocytes...
December 23, 2016: Blood
https://www.readbyqxmd.com/read/28002725/sifting-through-cd8-t-cell-memory
#12
Matthew D Martin, Vladimir P Badovinac
In this issue of Immunity, Gerlach et al. (2016) describe three distinct memory CD8(+) T cell subsets based upon expression of the fractalkine receptor CX3CR1. Their findings revise the paradigm of effector and central memory T cells by revealing a subset of CD8(+) memory T cells defined by intermediate levels of expression of CX3CR1 that conducts tissue surveillance.
December 20, 2016: Immunity
https://www.readbyqxmd.com/read/27974221/cell-based-delivery-of-interleukin-13-directs-alternative-activation-of%C3%A2-macrophages-resulting-in-improved-functional-outcome-after%C3%A2-spinal%C3%A2-cord%C3%A2-injury
#13
Dearbhaile Dooley, Evi Lemmens, Tim Vangansewinkel, Debbie Le Blon, Chloé Hoornaert, Peter Ponsaerts, Sven Hendrix
The therapeutic effects of mesenchymal stem cell (MSC) transplantation following spinal cord injury (SCI) to date have been limited. Therefore, we aimed to enhance the immunomodulatory properties of MSCs via continuous secretion of the anti-inflammatory cytokine interleukin-13 (IL-13). By using MSCs as carriers of IL-13 (MSC/IL-13), we investigated their therapeutic potential, compared with non-engineered MSCs, in a mouse model of SCI. We show that transplanted MSC/IL-13 significantly improve functional recovery following SCI, and also decrease lesion size and demyelinated area by more than 40%...
December 13, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27974048/selective-suppression-of-the-%C3%AE-isoform-of-p38-mapk-rescues-late-stage-tau-pathology
#14
Nicole Maphis, Shanya Jiang, Guixiang Xu, Olga N Kokiko-Cochran, Saktimayee M Roy, Linda J Van Eldik, D Martin Watterson, Bruce T Lamb, Kiran Bhaskar
BACKGROUND: Hyperphosphorylation and aggregation of tau protein are the pathological hallmarks of Alzheimer's disease and related tauopathies. We previously demonstrated that the microglial activation induces tau hyperphosphorylation and cognitive impairment via activation of p38 mitogen-activated protein kinase (p38 MAPK) in the hTau mouse model of tauopathy that was deficient for microglial fractalkine receptor CX3CR1. METHOD: We report an isoform-selective, brain-permeable, and orally bioavailable small molecule inhibitor of p38α MAPK (MW181) and its effects on tau phosphorylation in vitro and in hTau mice...
December 15, 2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27973687/the-therapeutic-potential-of-targeting-chemokine-signalling-in-the-treatment-of-chronic-pain
#15
REVIEW
Karli Montague, Marzia Malcangio
Chronic pain is a distressing condition, which is experienced even when the painful stimulus, whether surgery or disease-related, has subsided. Current treatments for chronic pain show limited efficacy and come with a host of undesirable side-effects, and thus there is a need for new, more effective therapies to be developed. The mechanisms underlying chronic pain are not fully understood at present, although preclinical models have facilitated the progress of this understanding considerably in the last decade...
December 14, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27966550/vaccination-for-mycobacterium-tuberculosis-infection-reprogramming-cd4-t-cell-homing-into-the-lung
#16
D L Barber
Development of effective tuberculosis vaccines is hampered by insufficient understanding of protective immunity. Here, Woodworth et al.(1) show secondary effector CD4 T cells generated after Mtb challenge of H56/CAF01 vaccinated mice display superior lung homing compared with primary effectors. Vaccination generates large populations of parenchymal lung effector cells by inducing CXCR3(+)KLRG1(-) cells that continuously migrate from lymph nodes to lung, and limiting the generation of non-protective CX3CR1(+)KLRG1(+) intravascular effectors, providing insight vaccine-mediated protection against tuberculosis...
December 14, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27942903/downregulation-of-cx3cr1-ameliorates-experimental-colitis-evidence-for-cx3cl1-cx3cr1-mediated-immune-cell-recruitment
#17
Felix Becker, Christina Holthoff, Christoph Anthoni, Emile Rijcken, J Steven Alexander, Felicity N E Gavins, H U Spiegel, Norbert Senninger, Thorsten Vowinkel
PURPOSE: Inflammatory conditions like inflammatory bowel diseases (IBD) are characterized by increased immune cell infiltration. The chemokine ligand CX3CL1 and its receptor CX3CR1 have been shown to be involved in leukocyte adhesion, transendothelial recruitment, and chemotaxis. Therefore, the objective of this study was to describe CX3CL1-CX3CR1-mediated signaling in the induction of immune cell recruitment during experimental murine colitis. METHODS: Acute colitis was induced by dextran sodium sulfate (DSS), and sepsis was induced by injection of lipopolysaccharide (LPS)...
December 10, 2016: International Journal of Colorectal Disease
https://www.readbyqxmd.com/read/27941884/emergent-role-of-the-fractalkine-axis-in-dissemination-of-peritoneal-metastasis-from-epithelial-ovarian-carcinoma
#18
H Gurler Main, J Xie, G G Muralidhar, O Elfituri, H Xu, A A Kajdacsy-Balla, M V Barbolina
Epithelial ovarian carcinoma is the most common cause of death from gynecologic cancers largely due to advanced, relapsed and chemotherapy-resistant peritoneal metastasis, which is refractory to the currently used treatment approaches. Mechanisms supporting advanced and relapsed peritoneal metastasis are largely unknown, precluding development of more effective targeted therapies. In this study, we investigated the function of a potentially targetable fractalkine axis in the formation and the development of advanced and relapsed peritoneal metastasis and its impact on patients' outcomes...
December 12, 2016: Oncogene
https://www.readbyqxmd.com/read/27939671/the-chemokine-receptor-cx3cr1-defines-three-antigen-experienced-cd8%C3%A2-t-cell-subsets-with-distinct-roles-in-immune-surveillance-and-homeostasis
#19
Carmen Gerlach, E Ashley Moseman, Scott M Loughhead, David Alvarez, Anthonie J Zwijnenburg, Lisette Waanders, Rohit Garg, Juan C de la Torre, Ulrich H von Andrian
Infections induce pathogen-specific T cell differentiation into diverse effectors (Teff) that give rise to memory (Tmem) subsets. The cell-fate decisions and lineage relationships that underlie these transitions are poorly understood. Here, we found that the chemokine receptor CX3CR1 identifies three distinct CD8(+) Teff and Tmem subsets. Classical central (Tcm) and effector memory (Tem) cells and their corresponding Teff precursors were CX3CR1(-) and CX3CR1(high), respectively. Viral infection also induced a numerically stable CX3CR1(int) subset that represented ∼15% of blood-borne Tmem cells...
December 20, 2016: Immunity
https://www.readbyqxmd.com/read/27936058/modeling-the-role-of-lanthionine-synthetase-c-like-2-lancl2-in-the-modulation-of-immune-responses-to-helicobacter-pylori-infection
#20
Andrew Leber, Josep Bassaganya-Riera, Nuria Tubau-Juni, Victoria Zoccoli-Rodriguez, Monica Viladomiu, Vida Abedi, Pinyi Lu, Raquel Hontecillas
Immune responses to Helicobacter pylori are orchestrated through complex balances of host-bacterial interactions, including inflammatory and regulatory immune responses across scales that can lead to the development of the gastric disease or the promotion of beneficial systemic effects. While inflammation in response to the bacterium has been reasonably characterized, the regulatory pathways that contribute to preventing inflammatory events during H. pylori infection are incompletely understood. To aid in this effort, we have generated a computational model incorporating recent developments in the understanding of H...
2016: PloS One
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