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https://www.readbyqxmd.com/read/28540528/sema3a-promotes-the-resolution-of-cardiac-inflammation-after-myocardial-infarction
#1
Marieke Rienks, Paolo Carai, Nicole Bitsch, Mark Schellings, Maarten Vanhaverbeke, Johan Verjans, Ilona Cuijpers, Stephane Heymans, Anna Papageorgiou
Optimal healing after myocardial infarction requires not only the induction of inflammation, but also its timely resolution. In patients, 30 days post myocardial infarction, circulating monocytes have increased expression of Semaphorin3A (Sema3A) as compared to directly after admission. This increased expression coincides with increased expression of Cx3CR1-a marker of non-classical monocytes that are important for immune resolution hence proper wound healing. In mice, the expression of Sema3A also increases in response to myocardial ischemia being expressed by infiltrating leukocytes...
July 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28528700/directed-differentiation-of-human-pluripotent-stem-cells-to-microglia
#2
Panagiotis Douvaras, Bruce Sun, Minghui Wang, Ilya Kruglikov, Gregory Lallos, Matthew Zimmer, Cecile Terrenoire, Bin Zhang, Sam Gandy, Eric Schadt, Donald O Freytes, Scott Noggle, Valentina Fossati
Microglia, the immune cells of the brain, are crucial to proper development and maintenance of the CNS, and their involvement in numerous neurological disorders is increasingly being recognized. To improve our understanding of human microglial biology, we devised a chemically defined protocol to generate human microglia from pluripotent stem cells. Myeloid progenitors expressing CD14/CX3CR1 were generated within 30 days of differentiation from both embryonic and induced pluripotent stem cells (iPSCs). Further differentiation of the progenitors resulted in ramified microglia with highly motile processes, expressing typical microglial markers...
May 18, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28522896/shear-stress-counteracts-endothelial-cx3cl1-induction-and-monocytic-cell-adhesion
#3
Aaron Babendreyer, Lisa Molls, Daniela Dreymueller, Stefan Uhlig, Andreas Ludwig
Flow conditions critically regulate endothelial cell functions in the vasculature. Reduced shear stress resulting from disturbed blood flow can drive the development of vascular inflammatory lesions. On endothelial cells, the transmembrane chemokine CX3CL1/fractalkine promotes vascular inflammation by functioning as a surface-expressed adhesion molecule and by becoming released as soluble chemoattractant for monocytic cells expressing the receptor CX3CR1. Here, we report that endothelial cells from human artery, vein, or microvasculature constitutively express CX3CL1 when cultured under static conditions...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28504723/cx3cr1-monocytes-modulate-learning-and-learning-dependent-dendritic-spine-remodeling-via-tnf-%C3%AE
#4
Juan Mauricio Garré, Hernandez Moura Silva, Juan J Lafaille, Guang Yang
Impaired learning and cognitive function often occurs during systemic infection or inflammation. Although activation of the innate immune system has been linked to the behavioral and cognitive effects that are associated with infection, the underlying mechanisms remain poorly understood. Here we mimicked viral immune activation with poly(I:C), a synthetic analog of double-stranded RNA, and longitudinally imaged postsynaptic dendritic spines of layer V pyramidal neurons in the mouse primary motor cortex using two-photon microscopy...
May 15, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28501330/virus-entry-and-replication-in-the-brain-precedes-blood-brain-barrier-disruption-during-intranasal-alphavirus-infection
#5
Matthew D Cain, Hamid Salimi, Yongfeng Gong, Lihua Yang, Samantha L Hamilton, James R Heffernan, Jianghui Hou, Mark J Miller, Robyn S Klein
Viral infections of the central nervous system (CNS) are often associated with blood-brain barrier (BBB) disruption, yet the impact of virus replication and immune cell recruitment on BBB integrity are incompletely understood. Using two-photon microscopy, we demonstrate that Venezuelan equine encephalitis virus (VEEV) strain TC83-GFP, a GFP expressing, attenuated strain with a G3A mutation within the 5' UTR that is associated with increased sensitivity to type I interferons (IFNs), does not directly impact BBB permeability...
May 1, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28487961/influence-of-aspirin-on-the-cx3cl1-cx3cr1-signaling-pathway-in-acute-pulmonary-embolism
#6
Zhirong Zhang, Weiji Yang, Rongbiao Ying, Ying Shi, Huifang Jiang, Danli Cai, Jing Kuang, Ruhui Yang, Lingcong Wang
The present study aimed to explore the influence of aspirin on the CX3CL1/CX3CR1 signaling pathway in acute pulmonary embolism (APE) in rats. Our previous study found that CX3CL1/CX3CR1 was increased in APE. However, the effect of this signaling pathway on APE remains unclear. CX3CL1-shRNA adenovirus and CX3CL1-overexpression vector were constructed. Male Sprague-Dawley rats were randomly divided into 9 groups (n=10): normal group (group N), sham operation group (group Sham), sham operation + aspirin group (group ASP), model group (group M), model + ASP group (group M+A), model + shRNA group (group M+SH), sham operation + CX3CL1-overexpression vector group (group Sham+Cx3), model + ASP + shRNA group (group M+A+SH), and model + ASP + CX3CL1-overexpression vector group (group M+A+CX3)...
April 26, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28472653/migrating-interneurons-secrete-fractalkine-to-promote-oligodendrocyte-formation-in-the-developing-mammalian-brain
#7
Anastassia Voronova, Scott A Yuzwa, Beatrix S Wang, Siraj Zahr, Charvi Syal, Jing Wang, David R Kaplan, Freda D Miller
During development, newborn interneurons migrate throughout the embryonic brain. Here, we provide evidence that these interneurons act in a paracrine fashion to regulate developmental oligodendrocyte formation. Specifically, we show that medial ganglionic eminence (MGE) interneurons secrete factors that promote genesis of oligodendrocytes from glially biased cortical precursors in culture. Moreover, when MGE interneurons are genetically ablated in vivo prior to their migration, this causes a deficit in cortical oligodendrogenesis...
May 3, 2017: Neuron
https://www.readbyqxmd.com/read/28464004/vitamin-d-deficiency-is-associated-with-il-6-levels-and-monocyte-activation-in-hiv-infected-persons
#8
Maura Manion, Katherine Huppler Hullsiek, Eleanor M P Wilson, Frank Rhame, Erna Kojic, David Gibson, John Hammer, Pragna Patel, John T Brooks, Jason V Baker, Irini Sereti
BACKGROUND: Immune activation plays a key role in HIV pathogenesis. Markers of inflammation have been associated with vitamin D deficiency in the general population. Studies have also demonstrated associations of vitamin D deficiency with increased risk of HIV progression and death. The relationship between persistent inflammation and immune activation during chronic HIV infection and vitamin D deficiency remains unclear. METHODS: Cryopreserved specimens were analyzed from 663 participants at the time of enrollment from the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN Study) from 2004 to 2006...
2017: PloS One
https://www.readbyqxmd.com/read/28462835/synthesis-and-preliminary-biological-evaluation-of-11-c-methyl-2-amino-5-benzylthio-thiazolo-4-5-d-pyrimidin-7-yl-d-leucinate-for-the-fractalkine-receptor-cx3cr1
#9
Mingzhang Gao, Min Wang, Jill A Meyer, Jonathan S Peters, Hamideh Zarrinmayeh, Paul R Territo, Gary D Hutchins, Qi-Huang Zheng
The reference standard methyl (2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-d-leucinate (5) and its precursor 2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-d-leucine (6) were synthesized from 6-amino-2-mercaptopyrimidin-4-ol and BnBr with overall chemical yield 7% in five steps and 4% in six steps, respectively. The target tracer [(11)C]methyl (2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-d-leucinate ([(11)C]5) was prepared from the acid precursor with [(11)C]CH3OTf through O-[(11)C]methylation and isolated by HPLC combined with SPE in 40-50% radiochemical yield, based on [(11)C]CO2 and decay corrected to end of bombardment (EOB)...
April 24, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28459435/brown-adipose-tissue-macrophages-control-tissue-innervation-and-homeostatic-energy-expenditure
#10
Yochai Wolf, Sigalit Boura-Halfon, Nina Cortese, Zhana Haimon, Hadas Sar Shalom, Yael Kuperman, Vyacheslav Kalchenko, Alexander Brandis, Eyal David, Yifat Segal-Hayoun, Louise Chappell-Maor, Avraham Yaron, Steffen Jung
Tissue macrophages provide immunological defense and contribute to the establishment and maintenance of tissue homeostasis. Here we used constitutive and inducible mutagenesis to delete the nuclear transcription regulator Mecp2 in macrophages. Mice that lacked the gene encoding Mecp2, which is associated with Rett syndrome, in macrophages did not show signs of neurodevelopmental disorder but displayed spontaneous obesity, which was linked to impaired function of brown adipose tissue (BAT). Specifically, mutagenesis of a BAT-resident Cx3Cr1(+) macrophage subpopulation compromised homeostatic thermogenesis but not acute, cold-induced thermogenesis...
June 2017: Nature Immunology
https://www.readbyqxmd.com/read/28459434/mice-deficient-in-nrros-show-abnormal-microglial-development-and-neurological-disorders
#11
Kit Wong, Rajkumar Noubade, Paolo Manzanillo, Naruhisa Ota, Oded Foreman, Jason A Hackney, Brad A Friedman, Rajita Pappu, Kimberly Scearce-Levie, Wenjun Ouyang
Microglia and other tissue-resident macrophages within the central nervous system (CNS) have essential roles in neural development, inflammation and homeostasis. However, the molecular pathways underlying their development and function remain poorly understood. Here we report that mice deficient in NRROS, a myeloid-expressed transmembrane protein in the endoplasmic reticulum, develop spontaneous neurological disorders. NRROS-deficient (Nrros(-/-)) mice show defects in motor functions and die before 6 months of age...
May 1, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28450294/gas6-growth-arrest-specific-6-promotes-inflammatory-ccr2-hi-cx3cr1-lo-monocyte-recruitment-in-venous-thrombosis
#12
Sandrine Laurance, François-René Bertin, Talin Ebrahimian, Yusra Kassim, Ryan N Rys, Stéphanie Lehoux, Catherine A Lemarié, Mark D Blostein
OBJECTIVES: Coagulation and inflammation are inter-related. Gas6 (growth arrest-specific 6) promotes venous thrombosis and participates to inflammation through endothelial-innate immune cell interactions. Innate immune cells can provide the initiating stimulus for venous thrombus development. We hypothesize that Gas6 promotes monocyte recruitment during venous thrombosis. APPROACH AND RESULTS: Deep venous thrombosis was induced in wild-type and Gas6-deficient (-/-) mice using 5% FeCl3 and flow reduction in the inferior vena cava...
April 27, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28446866/the-contribution-of-immune-infiltrates-to-ototoxicity-and-cochlear-hair-cell-loss
#13
REVIEW
Megan B Wood, Jian Zuo
Cells of the immune system have been shown to infiltrate the cochlea after acoustic trauma or ototoxic drug treatment; however, the contribution of the immune system to hair cell loss in the inner ear is incompletely understood. Most studies have concentrated on the immediate innate response to hair cell damage using CD45 as a broad marker for all immune cells. More recent studies have used RNA sequencing, GeneChip arrays and quantitative PCR to analyze gene expression in the entire cochlea after auditory trauma, leading to a better understanding of the chemokines and cytokines that attract immune cells to the cochlea...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28439004/endocannabinoid-system-acts-as-a-regulator-of-immune-homeostasis-in-the-gut
#14
Nandini Acharya, Sasi Penukonda, Tatiana Shcheglova, Adam T Hagymasi, Sreyashi Basu, Pramod K Srivastava
Endogenous cannabinoids (endocannabinoids) are small molecules biosynthesized from membrane glycerophospholipid. Anandamide (AEA) is an endogenous intestinal cannabinoid that controls appetite and energy balance by engagement of the enteric nervous system through cannabinoid receptors. Here, we uncover a role for AEA and its receptor, cannabinoid receptor 2 (CB2), in the regulation of immune tolerance in the gut and the pancreas. This work demonstrates a major immunological role for an endocannabinoid. The pungent molecule capsaicin (CP) has a similar effect as AEA; however, CP acts by engagement of the vanilloid receptor TRPV1, causing local production of AEA, which acts through CB2...
May 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28438899/galectin-3-a-positive-regulator-of-leukocyte-recruitment-in-the-inflamed-microcirculation
#15
Beatrice R Gittens, Jennifer V Bodkin, Sussan Nourshargh, Mauro Perretti, Dianne Cooper
In vivo and ex vivo imaging were used to investigate the function of galectin-3 (Gal-3) during the process of leukocyte recruitment to the inflamed microcirculation. The cremasteric microcirculation of wild-type (C57BL/6), Gal-3(-/-), and CX3CR1(gfp/+) mice were assessed by intravital microscopy after PBS, IL-1β, TNF-α, or recombinant Gal-3 treatment. These cellular responses were investigated further using flow-chamber assays, confocal microscopy, flow cytometry, PCR analysis, and proteome array. We show that mechanisms mediating leukocyte slow rolling and emigration are impaired in Gal-3(-/-) mice, which could be because of impaired expression of cell adhesion molecules and an altered cell surface glycoproteome...
June 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28421250/erratum-to-cx3cr1-deficiency-accelerates-the-development-of-retinopathy-in-a-rodent-model-of-type-1-diabetes
#16
Eleni Beli, James M Dominguez, Ping Hu, Jeffrey S Thinschmidt, Sergio Caballero, Sergio Li Calzi, Defang Luo, Sumathi Shanmugam, Tatiana E Salazar, Yaqian Duan, Michael E Boulton, Susanna Mohr, Steven F Abcouwer, Daniel R Saban, Jeffrey K Harrison, Maria B Grant
No abstract text is available yet for this article.
April 18, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28407008/dysregulated-signaling-proliferation-and-apoptosis-impact-on-the-pathogenesis-of-tcr%C3%AE-%C3%AE-t-cell-large-granular-lymphocyte-leukemia
#17
Martine J Kallemeijn, Dick de Ridder, Joyce Schilperoord-Vermeulen, Michèle Y van der Klift, Yorick Sandberg, Jacques J M van Dongen, Anton W Langerak
TCRγδ+ T-LGL leukemia is a rare form of chronic mature T cell disorders in elderly, which is generally characterized by a persistently enlarged CD3+CD57+TCRγδ+ large granular lymphocyte population in the peripheral blood with a monoclonal phenotype. Clinically, the disease is heterogeneous, most patients being largely asymptomatic, although neutropenia, fatigue and B symptoms and underlying diseases such as autoimmune diseases or malignancies are also often observed. The etiology of TCRγδ+ T-LGL proliferations is largely unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28405903/stress-induced-alterations-of-immune-profile-in-animals-suffering-by-tau-protein-driven-neurodegeneration
#18
Petr Novak, Martin Cente, Nina Kosikova, Tomas Augustin, Richard Kvetnansky, Michal Novak, Peter Filipcik
Alzheimer's disease (AD) is a multifactorial disorder; neurofibrillary pathology composed of tau protein is found side by side with amyloid-β deposits and extensive neuroinflammation. The immune system of the brain is considered as one of the factors that could influence the speed of the progression of AD neuropathology as a potential mediator of the damage induced by AD protein deposits. Alzheimer's disease pathology can be impacted by psychological stress; however, signalling pathways in background are not well known...
April 12, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28398520/injury-leads-to-the-appearance-of-cells-with-characteristics-of-both-microglia-and-astrocytes-in-mouse-and-human-brain
#19
Ulrika Wilhelmsson, Daniel Andersson, Yolanda de Pablo, Roy Pekny, Anders Ståhlberg, Jan Mulder, Nicholas Mitsios, Tibor Hortobágyi, Milos Pekny, Marcela Pekna
Microglia and astrocytes have been considered until now as cells with very distinct identities. Here, we assessed the heterogeneity within microglia/monocyte cell population in mouse hippocampus and determined their response to injury, by using single-cell gene expression profiling of cells isolated from uninjured and deafferented hippocampus. We found that in individual cells, microglial markers Cx3cr1, Aif1, Itgam, and Cd68 were co-expressed. Interestingly, injury led to the co-expression of the astrocyte marker Gfap in a subpopulation of Cx3cr1-expressing cells from both the injured and contralesional hippocampus...
April 7, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28392788/the-transcription-factor-hobit-identifies-human-cytotoxic-cd4-t-cells
#20
Anna E Oja, Felipe A Vieira Braga, Ester B M Remmerswaal, Natasja A M Kragten, Kirsten M L Hertoghs, Jianmin Zuo, Paul A Moss, René A W van Lier, Klaas P J M van Gisbergen, Pleun Hombrink
The T cell lineage is commonly divided into CD4-expressing helper T cells that polarize immune responses through cytokine secretion and CD8-expressing cytotoxic T cells that eliminate infected target cells by virtue of the release of cytotoxic molecules. Recently, a population of CD4(+) T cells that conforms to the phenotype of cytotoxic CD8(+) T cells has received increased recognition. These cytotoxic CD4(+) T cells display constitutive expression of granzyme B and perforin at the protein level and mediate HLA class II-dependent killing of target cells...
2017: Frontiers in Immunology
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