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    Glycosylphosphatidylinositol (GPI) anchored protein deficiency serves as a reliable reporter of Pig-a gene Mutation: Support from an in vitro assay based on L5178Y/Tk(+/-) cells and the CD90.2 antigen.
    Environ Mol Mutagen 2017 Nov 8. Epub 2017 Nov 8.
    Litron Laboratories, Rochester, New York.
    Lack of cell surface glycosylphosphatidylinositol (GPI)-anchored protein(s) has been used as a reporter of Pig-a gene mutation in several model systems. As an extension of this work, our laboratory initiated development of an in vitro mutation assay based on the flow cytometric assessment of CD90.2 expression on the cell surface of the mouse lymphoma cell line L5178Y/Tk(+/-) . Read More

    Circadian clock cryptochrome proteins regulate autoimmunity.
    Proc Natl Acad Sci U S A 2017 Nov 6;114(47):12548-12553. Epub 2017 Nov 6.
    Department of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, CA 90048.
    The circadian system regulates numerous physiological processes including immune responses. Here, we show that mice deficient of the circadian clock genes Cry1 and Cry2 [Cry double knockout (DKO)] develop an autoimmune phenotype including high serum IgG concentrations, serum antinuclear antibodies, and precipitation of IgG, IgM, and complement 3 in glomeruli and massive infiltration of leukocytes into the lungs and kidneys. Flow cytometry of lymphoid organs revealed decreased pre-B cell numbers and a higher percentage of mature recirculating B cells in the bone marrow, as well as increased numbers of B2 B cells in the peritoneal cavity of Cry DKO mice. Read More

    Autoantibodies against complement components in systemic lupus erythematosus - role in the pathogenesis and clinical manifestations.
    Lupus 2017 Dec 18;26(14):1550-1555. Epub 2017 May 18.
    2 Department of Chemistry, Biochemistry, Physiology and Pathophysiology, Sofia University "St. Kliment Ohridski", Bulgaria.
    Many complement structures and a number of additional factors, i.e. autoantibodies, receptors, hormones and cytokines, are implicated in the complex pathogenesis of systemic lupus erythematosus. Read More

    Spred2-deficiecy Protects Mice from Polymicrobial Septic Peritonitis by Enhancing Inflammation and Bacterial Clearance.
    Sci Rep 2017 Oct 9;7(1):12833. Epub 2017 Oct 9.
    Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, 700-8558, Japan.
    Sepsis is an infection-induced systemic inflammatory syndrome and a major cause of death for critically ill patients. Here, we examined whether the absence of Sprouty-related EVH1-domain-containing protein 2 (Spred2), a negative regulator of the Ras/Raf/ERK/MAPK pathway, influences host defense against polymicrobial sepsis (PMS) induced by cecal ligation and puncture (CLP). Compared to wild-type mice, Spred2(-/-) mice exhibited higher survival rates with increased level of leukocyte infiltration and local chemokine production and reduced plasma and peritoneal bacterial loads after CLP. Read More

    An ABC of the Warning Signs of Hereditary Angioedema.
    Int Arch Allergy Immunol 2017 27;174(1):1-6. Epub 2017 Sep 27.
    Faculdade de Medicina ABC, Santo Andre, Brazil.
    Hereditary angioedema (HAE) with C1 inhibitor deficiency is a genetic disorder that clinically manifests with attacks of angioedema in the subcutaneous and submucosal tissues, mainly in the extremities, abdomen, and upper airway. During attacks, vascular permeability is increased due to increased bradykinin (BK). This means that special therapies are needed for attacks that do not respond to traditional antiallergic therapies involving antihistamines, corticosteroids, and epinephrine. Read More

    Complement C5a receptors C5L2 and C5aR in renal fibrosis.
    Am J Physiol Renal Physiol 2017 Sep 13:ajprenal.00060.2017. Epub 2017 Sep 13.
    Saarland University Medical Center.
    Complement factor C5a has two known receptors, C5aR mediating pro-inflammatory effects and C5L2, a potential C5a scavenger. We previously identified C5a/C5aR signaling as a potent profibrotic pathway in the kidney. Here we tested for the first time the role of C5L2 in renal fibrosis. Read More

    CD18 deficiency improves liver injury in the MCD model of steatohepatitis.
    PLoS One 2017 5;12(9):e0183912. Epub 2017 Sep 5.
    Department of Medicine, University of California, San Francisco, San Francisco, California, United States of America.
    Neutrophils and macrophages are important constituents of the hepatic inflammatory infiltrate in non-alcoholic steatohepatitis. These innate immune cells express CD18, an adhesion molecule that facilitates leukocyte activation. In the context of fatty liver, activation of infiltrated leukocytes is believed to enhance hepatocellular injury. Read More

    IgG is elevated in obese white adipose tissue but does not induce glucose intolerance via Fcγ-receptor or complement.
    Int J Obes (Lond) 2017 Aug 30. Epub 2017 Aug 30.
    Einthoven Laboratory for Experimental Vascular Medicine, Leiden, The Netherlands.
    Background/objectives: In obesity, B cells accumulate in white adipose tissue (WAT) and produce IgG, which may contribute to the development of glucose intolerance. IgG signals by binding to Fcγ receptors (FcγR) and by activating the complement system. The aim of our study was to investigate whether activation of FcγR and/or complement C3 mediates the development of high-fat diet-induced glucose intolerance. Read More

    IL-17A deficiency mitigates bleomycin-induced complement activation during lung fibrosis.
    FASEB J 2017 Aug 17. Epub 2017 Aug 17.
    Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan, USA;
    Interleukin 17A (IL-17A) and complement (C') activation have each been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). We have reported that IL-17A induces epithelial injury via TGF-β in murine bronchiolitis obliterans; that TGF-β and the C' cascade present signaling interactions in mediating epithelial injury; and that the blockade of C' receptors mitigates lung fibrosis. In the present study, we investigated the role of IL-17A in regulating C' in lung fibrosis. Read More

    The atypical receptor CCRL2 is required for CXCR2-dependent neutrophil recruitment and tissue damage.
    Blood 2017 Sep 25;130(10):1223-1234. Epub 2017 Jul 25.
    Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
    CCRL2 is a 7-transmembrane domain receptor that shares structural and functional similarities with the family of atypical chemokine receptors (ACKRs). CCRL2 is upregulated by inflammatory signals and, unlike other ACKRs, it is not a chemoattractant-scavenging receptor, does not activate β-arrestins, and is widely expressed by many leukocyte subsets. Therefore, the biological role of CCRL2 in immunity is still unclear. Read More

    Anti-Neu5Gc and anti-non-Neu5Gc antibodies in healthy humans.
    PLoS One 2017 17;12(7):e0180768. Epub 2017 Jul 17.
    Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, United States of America.
    Our group previously investigated the levels of anti-Gal and anti-nonGal IgM and IgG in a cohort of 75 healthy humans of various backgrounds, and found some significant differences related to factors such as age, gender, ABO blood group, diet, vaccination history, and geographic location during childhood. We have now expanded our cohort (n = 84) to investigate the levels of anti-Neu5Gc and anti-nonGal/nonNeu5Gc antibodies in healthy humans. Anti-nonGal and anti-nonGal/nonNeu5Gc human IgM and IgG binding to pRBCs and pAECs from GTKO/CD46 and GTKO/CD46/Neu5GcKO pigs were measured by flow cytometry. Read More

    Increased aggression and lack of maternal behavior in Dio3-deficient mice are associated with abnormalities in oxytocin and vasopressin systems.
    Genes Brain Behav 2017 Jul 17. Epub 2017 Jul 17.
    Maine Medical Center Research Institute, Center for Molecular Medicine, Scarborough, ME, USA.
    Thyroid hormones regulate many aspects of brain development and function, and alterations in the levels of thyroid hormone action lead to abnormal anxiety- and depression-like behaviors. A complement of factors in the brain function independently of circulating levels of hormone to strictly controlled local thyroid hormone signaling. A critical factor is the type 3 deiodinase (DIO3), which is located in neurons and protects the brain from excessive thyroid hormone. Read More

    Circulating dsDNA, endothelial injury, and complement activation in thrombotic microangiopathy and GVHD.
    Blood 2017 Sep 13;130(10):1259-1266. Epub 2017 Jul 13.
    Division of Bone Marrow Transplantation and Immune Deficiency and.
    Transplant-associated thrombotic microangiopathy (TA-TMA) is a common and poorly recognized complication of hematopoietic stem cell transplantation (HSCT) associated with excessive complement activation, likely triggered by endothelial injury. An important missing piece is the link between endothelial injury and complement activation. We hypothesized that neutrophil extracellular traps (NETs) mechanistically link endothelial damage with complement activation and subsequent TA-TMA. Read More

    Interferon Regulatory Factor 5 Controls Necrotic Core Formation in Atherosclerotic Lesions by Impairing Efferocytosis.
    Circulation 2017 Sep 11;136(12):1140-1154. Epub 2017 Jul 11.
    From Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, United Kingdom (A.N.S., A.E., J.E.C., C.K., M.S., I.P., P.G., T.K., D.S., M.E.G., S.N.S., I.A.U., C.M.); Department of Bioengineering, Imperial College London, United Kingdom (A.N.S., R.K.); Experimental Cardiovascular Research Unit, Clinical Research Centre, Clinical Sciences Malmö, Lund University, Sweden (A.E., I.G.); Department of Cardiology, Skåne University Hospital, Lund/Malmö, Sweden (A.E., I.G.); and School of Engineering and Materials Science, Queen Mary University of London, United Kingdom (R.K.).
    Background: Myeloid cells are central to atherosclerotic lesion development and vulnerable plaque formation. Impaired ability of arterial phagocytes to uptake apoptotic cells (efferocytosis) promotes lesion growth and establishment of a necrotic core. The transcription factor interferon regulatory factor (IRF)-5 is an important modulator of myeloid function and programming. Read More

    Interferon-β regulates dendritic cell activation and migration in experimental autoimmune encephalomyelitis.
    Immunology 2017 Nov 21;152(3):439-450. Epub 2017 Jul 21.
    Toronto General Research Institute, University Health Network, Toronto, ON, Canada.
    CD11c(+) dendritic cells (DCs) exert a critical role as antigen-presenting cells in regulating pathogenic T cells in multiple sclerosis (MS). To determine whether the therapeutic benefit of interferon-β (IFN-β) treatment for MS is in part influenced by IFN regulation of DC function, we examined the immunophenotype of DCs derived from IFN-β(+/+) and IFN-β(-/-) mice using a myelin oligodendrocyte glycoprotein (MOG) peptide-induced mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Our earlier work identified that IFN-β(-/-) mice exhibit earlier onset and more rapid progression of neurological impairment compared with IFN-β(+/+) mice. Read More

    MECHANISMS OF COIX SEED COMPOSITIONS IN THE TREATMENT OF SPLEEN DEFICIENCY AND WET DAMPNESS ZHENG.
    Afr J Tradit Complement Altern Med 2017 5;14(4):239-246. Epub 2017 Jun 5.
    College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.
    Background: Coix seed has the functions of fortifying the spleen and inhibiting the dampness. However, it remains unclear which Coix seed compositions is responsible for these functions. Previous investigations have revealed that the main compositions of Coix seed are proteins, polysaccharides, oils and starches. Read More

    Measurement of Aortic Cell Fluid-Phase Pinocytosis in vivo by Flow Cytometry.
    J Vasc Res 2017 16;54(4):195-199. Epub 2017 Jun 16.
    Section of Experimental Atherosclerosis, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.
    Objective: Fluid-phase pinocytosis is a receptor-independent mechanism of endocytosis that occurs in all mammalian cells and may be a mechanism for the uptake of LDL by macrophages. As there are currently no methods for the measurement of fluid-phase pinocytosis by individual aortic cells in vivo, we sought to identify a suitable method.

    Methods: ApoE-/- mice were retro-orbitally injected with AngioSPARK fluorescent nanoparticles specifically designed to not interact with cells. Read More

    Glycolipids: Essential regulator of neuro-inflammation, metabolism and gliomagenesis.
    Biochim Biophys Acta 2017 10 7;1861(10):2479-2484. Epub 2017 Jun 7.
    Department of Biomedical Sciences, Chubu University College of Life and Health, 1200 Matsumoto, Kasugai, Aichi 487-8501, Japan; Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan.
    Gene knockout mice of glycosyltransferases have clearly showed roles of their products in the bodies, while there are examples where phenotype of knockout was much less severe than expected probably due to functional redundancy. The most striking novel finding obtained from ganglioside-deficient mice was that progressive inflammatory reaction took place, leading to neurodegeneration. In particular, dysfunction of complement-regulatory proteins due to deteriorated architecture of lipid rafts seemed to be essential mechanisms for the inflammation. Read More

    Complement C5a induces mesenchymal stem cell apoptosis during the progression of chronic diabetic complications.
    Diabetologia 2017 Jun 3. Epub 2017 Jun 3.
    First Department, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital and Research Institute of Surgery, Third Military Medical University, No. 10 Changjiang Branch Road, Daping Street, Yuzhong District, Chongqing, 400042, People's Republic of China.
    Aims/hypothesis: Regeneration and repair mediated by mesenchymal stem cells (MSCs) are key self-protection mechanisms against diabetic complications, a reflection of diabetes-related cell/tissue damage and dysfunction. MSC abnormalities have been reported during the progression of diabetic complications, but little is known about whether a deficiency in these cells plays a role in the pathogenesis of this disease. In addition to MSC resident sites, peripheral circulation is a major source of MSCs that participate in the regeneration and repair of damaged tissue. Read More

    Cyp2c44 gene disruption is associated with increased hematopoietic stem cells: implication in chronic hypoxia-induced pulmonary hypertension.
    Am J Physiol Heart Circ Physiol 2017 Aug 26;313(2):H293-H303. Epub 2017 May 26.
    Department of Pharmacology, and Translation Cardiovascular Institute, School of Medicine, New York Medical College, Valhalla, New York;
    We have recently demonstrated that disruption of the murine cytochrome P-450 2c44 gene (Cyp2c44) exacerbates chronic hypoxia-induced pulmonary artery remodeling and hypertension in mice. Subsequently, we serendipitously found that Cyp2c44 gene disruption also increases hematopoietic stem cell (HSC) numbers in bone marrow and blood. Therefore, the objective of the present study was to investigate whether CYP2C44-derived eicosanoids regulate HSC proliferation/cell growth and whether increased HSCs contribute to chronic hypoxia-induced remodeling of pulmonary arteries in Cyp2c44 knockout mice. Read More

    The Upregulation of Integrin αDβ2 (CD11d/CD18) on Inflammatory Macrophages Promotes Macrophage Retention in Vascular Lesions and Development of Atherosclerosis.
    J Immunol 2017 Jun 12;198(12):4855-4867. Epub 2017 May 12.
    Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37604;
    Macrophage accumulation is a critical step during development of chronic inflammation, initiating progression of many devastating diseases. Leukocyte-specific integrin αDβ2 (CD11d/CD18) is dramatically upregulated on macrophages at inflammatory sites. Previously we found that CD11d overexpression on cell surfaces inhibits in vitro cell migration due to excessive adhesion. Read More

    Recurrent respiratory tract infections (RRTI) in the elderly: A late onset mild immunodeficiency?
    Clin Immunol 2017 Jul 6;180:111-119. Epub 2017 May 6.
    Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
    Elderly with late-onset recurrent respiratory tract infections (RRTI) often have specific anti-polysaccharide antibody deficiency (SPAD). We hypothesized that late-onset RRTI is caused by mild immunodeficiencies, such as SPAD, that remain hidden through adult life. We analyzed seventeen elderly RRTI patients and matched controls. Read More

    Peripheral complement interactions with amyloid β peptide: Erythrocyte clearance mechanisms.
    Alzheimers Dement 2017 May 2. Epub 2017 May 2.
    Center for Neuroscience, SRI International, Menlo Park, CA, USA. Electronic address:
    Introduction: Although amyloid β peptide (Aβ) is cleared from the brain to cerebrospinal fluid and the peripheral circulation, mechanisms for its removal from blood remain unresolved. Primates have uniquely evolved a highly effective peripheral clearance mechanism for pathogens, immune adherence, in which erythrocyte complement receptor 1 (CR1) plays a major role.

    Methods: Multidisciplinary methods were used to demonstrate immune adherence capture of Aβ by erythrocytes and its deficiency in Alzheimer's disease (AD). Read More

    Dysregulated CD46 shedding interferes with Th1-contraction in systemic lupus erythematosus.
    Eur J Immunol 2017 Jul 22;47(7):1200-1210. Epub 2017 May 22.
    Division of Genetics and Molecular Medicine, Department of Medical and Molecular Genetics, King's College London, Guy's Hospital, London, UK.
    IFN-γ-producing T helper 1 (Th1) cell responses mediate protection against infections but uncontrolled Th1 activity also contributes to a broad range of autoimmune diseases. Autocrine complement activation has recently emerged as key in the induction and contraction of human Th1 immunity: activation of the complement regulator CD46 and the C3aR expressed by CD4(+) T cells via autocrine generated ligands C3b and C3a, respectively, are critical to IFN-γ production. Further, CD46-mediated signals also induce co-expression of immunosuppressive IL-10 in Th1 cells and transition into a (self)-regulating and contracting phase. Read More

    C1q-Dependent Dendritic Cell Cross-Presentation of In Vivo-Formed Antigen-Antibody Complexes.
    J Immunol 2017 Jun 21;198(11):4235-4243. Epub 2017 Apr 21.
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 RC Leiden, the Netherlands;
    Dendritic cells (DCs) are specialized in Ag engulfment via a wide variety of uptake receptors on their cell surface. In the present study we investigated Ag uptake and presentation of in vivo-formed Ag-Ab complexes by i.v. Read More

    P2X1, P2X4, and P2X7 Receptor Knock Out Mice Expose Differential Outcome of Sepsis Induced by α-Haemolysin Producing Escherichia coli.
    Front Cell Infect Microbiol 2017 6;7:113. Epub 2017 Apr 6.
    Department of Biomedicine, Aarhus UniversityAarhus, Denmark.
    α-haemolysin (HlyA)-producing Escherichia coli commonly inflict severe urinary tract infections, including pyelonephritis, which comprises substantial risk for sepsis. In vitro, the cytolytic effect of HlyA is mainly mediated by ATP release through the HlyA pore and subsequent P2X1/P2X7 receptor activation. This amplification of the lytic process is not unique to HlyA but is observed by many other pore-forming proteins including complement-induced haemolysis. Read More

    HVC1 ameliorates hyperlipidemia and inflammation in LDLR(-/-) mice.
    BMC Complement Altern Med 2017 Apr 20;17(1):222. Epub 2017 Apr 20.
    College of Korean Medicine, Sangji University, Wonju-si, Gangwon-do, 26339, Republic of Korea.
    Background: HVC1 consists of Coptidis Rhizoma (dried rhizome of Coptischinensis), Scutellariae Radix (root of Scutellariabaicalensis), Rhei Rhizoma (rhizome of Rheum officinale), and Pruni Cortex (cortex of Prunusyedoensis Matsum). Although the components are known to be effective in various conditions such as inflammation, hypertension, and hypercholesterolemia, there are no reports of the molecular mechanism of its hypolipidemic effects.

    Methods: We investigated the hypolipidemic effect of HVC1 in low-density lipoprotein receptor-deficient (LDLR(-/-)) mice fed a high-cholesterol diet for 13 weeks. Read More

    SLAMF7 is critical for phagocytosis of haematopoietic tumour cells via Mac-1 integrin.
    Nature 2017 04 19;544(7651):493-497. Epub 2017 Apr 19.
    Laboratory of Molecular Oncology, Institut de recherches cliniques de Montréal (IRCM), Montréal, Québec H2W 1R7, Canada.
    Cancer cells elude anti-tumour immunity through multiple mechanisms, including upregulated expression of ligands for inhibitory immune checkpoint receptors. Phagocytosis by macrophages plays a critical role in cancer control. Therapeutic blockade of signal regulatory protein (SIRP)-α, an inhibitory receptor on macrophages, or of its ligand CD47 expressed on tumour cells, improves tumour cell elimination in vitro and in vivo, suggesting that blockade of the SIRPα-CD47 checkpoint could be useful in treating human cancer. Read More

    Critical role for complement receptor C5aR2 in the pathogenesis of renal ischemia-reperfusion injury.
    FASEB J 2017 Jul 10;31(7):3193-3204. Epub 2017 Apr 10.
    Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands;
    The complement system, and specifically C5a, is involved in renal ischemia-reperfusion (IR) injury. The 2 receptors for complement anaphylatoxin C5a (C5aR1 and C5aR2) are expressed on leukocytes as well as on renal epithelium. Extensive evidence shows that C5aR1 inhibition protects kidneys from IR injury; however, the role of C5aR2 in IR injury is less clear as initial studies proposed the hypothesis that C5aR2 functions as a decoy receptor. Read More

    Skin inflammation induced by lupus serum was inhibited in IL-1R deficient mice.
    Clin Immunol 2017 Jul 7;180:63-68. Epub 2017 Apr 7.
    Key Laboratory of Antibody Techniques of Ministry of Health, Nanjing Medical University, Nanjing, China; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China. Electronic address:
    Skin inflammation induced by lupus serum is a useful tool to investigate the pathogenesis of lupus skin injury. IL-1 is a proinflammatory cytokine, and its role in lupus skin lesion is still unclear. We determined the role of IL-1 in lupus skin injury by using gene deficient mice. Read More

    Common genetic variants are associated with lower serum 25-hydroxyvitamin D concentrations across the year among children at northern latitudes.
    Br J Nutr 2017 Mar 6;117(6):829-838. Epub 2017 Apr 6.
    2Department of Nutrition, Exercise and Sports, Faculty of Science,University of Copenhagen,Rolighedsvej 26,DK-1958 Frederiksberg C,Denmark.
    In a longitudinal study including 642 healthy 8-11-year-old Danish children, we investigated associations between vitamin D dependent SNP and serum 25-hydroxyvitamin D (25(OH)D) concentrations across a school year (August-June). Serum 25(OH)D was measured three times for every child, which approximated measurements in three seasons (autumn, winter, spring). Dietary and supplement intake, physical activity, BMI and parathyroid hormone were likewise measured at each time point. Read More

    Systematic analysis of splicing defects in selected primary immunodeficiencies-related genes.
    Clin Immunol 2017 Jul 27;180:33-44. Epub 2017 Mar 27.
    Central European Institute of Technology, Masaryk University, Brno, Czech Republic; Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation, Brno, Czech Republic; Institute of Clinical Immunology and Allergology, St. Anne's University Hospital and Masaryk University, Brno, Czech Republic. Electronic address:
    Both variants affecting splice sites and those in splicing regulatory elements (SREs) can impair pre-mRNA splicing, eventually leading to severe diseases. Despite the availability of many prediction tools, prognosis of splicing affection is not trivial, especially when SREs are involved. Here, we present data on 92 in silico-/55 minigene-analysed variants detected in genes responsible for the primary immunodeficiencies development (namely BTK, CD40LG, IL2RG, SERPING1, STAT3, and WAS). Read More

    RGC-32 Promotes Th17 Cell Differentiation and Enhances Experimental Autoimmune Encephalomyelitis.
    J Immunol 2017 May 29;198(10):3869-3877. Epub 2017 Mar 29.
    Research Service, Veteran Affairs Medical Center, Baltimore, MD 21201.
    Th17 cells play a critical role in autoimmune diseases, including multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis. Response gene to complement (RGC)-32 is a cell cycle regulator and a downstream target of TGF-β that mediates its profibrotic activity. In this study, we report that RGC-32 is preferentially upregulated during Th17 cell differentiation. Read More

    Reduced PU.1 expression underlies aberrant neutrophil maturation and function in β-thalassemia mice and patients.
    Blood 2017 Jun 21;129(23):3087-3099. Epub 2017 Mar 21.
    Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, VIC, Australia.
    β-Thalassemia is associated with several abnormalities of the innate immune system. Neutrophils in particular are defective, predisposing patients to life-threatening bacterial infections. The molecular and cellular mechanisms involved in impaired neutrophil function remain incompletely defined. Read More

    Analysis of monocyte infiltration in MPTP mice reveals that microglial CX3CR1 protects against neurotoxic over-induction of monocyte-attracting CCL2 by astrocytes.
    J Neuroinflammation 2017 Mar 21;14(1):60. Epub 2017 Mar 21.
    Inserm, U 1127, F-75013, Paris, France.
    Background: Evidence from mice suggests that brain infiltrating immune cells contribute to neurodegeneration, and we previously identified a deleterious lymphocyte infiltration in Parkinson's disease mice. However, this remains controversial for monocytes, due to artifact-prone techniques used to distinguish them from microglia. Our aim was to reassess this open question, by taking advantage of the recent recognition that chemokine receptors CCR2 and CX3CR1 can differentiate between inflammatory monocytes and microglia, enabling to test whether CCR2(+) monocytes infiltrate the brain during dopaminergic (DA) neurodegeneration and whether they contribute to neuronal death. Read More

    Myeloid C/EBPβ deficiency reshapes microglial gene expression and is protective in experimental autoimmune encephalomyelitis.
    J Neuroinflammation 2017 Mar 16;14(1):54. Epub 2017 Mar 16.
    Department of Biomedicine, Biochemistry and Molecular Biology Unit, School of Medicine, University of Barcelona, IDIBAPS, Barcelona, Spain.
    Background: CCAAT/enhancer binding protein β (C/EBPβ) is a transcription factor that regulates the expression of important pro-inflammatory genes in microglia. Mice deficient for C/EBPβ show protection against excitotoxic and ischemic CNS damage, but the involvement in this neuroprotective effect of the various C/EBPβ-expressing cell types is not solved. Since C/EBPβ-deficient microglia show attenuated neurotoxicity in culture, we hypothesized that specific C/EBPβ deficiency in microglia could be neuroprotective in vivo. Read More

    Synergy between the classical and alternative pathways of complement is essential for conferring effective protection against the pandemic influenza A(H1N1) 2009 virus infection.
    PLoS Pathog 2017 Mar 16;13(3):e1006248. Epub 2017 Mar 16.
    National Centre for Cell Science, S. P. Pune University Campus, Ganeshkhind, Pune, India.
    The pandemic influenza A(H1N1) 2009 virus caused significant morbidity and mortality worldwide thus necessitating the need to understand the host factors that influence its control. Previously, the complement system has been shown to provide protection during the seasonal influenza virus infection, however, the role of individual complement pathways is not yet clear. Here, we have dissected the role of intact complement as well as of its individual activation pathways during the pandemic influenza virus infection using mouse strains deficient in various complement components. Read More

    Targeting C3a/C5a receptors inhibits human mesangial cell proliferation and alleviates immunoglobulin A nephropathy in mice.
    Clin Exp Immunol 2017 Jul 10;189(1):60-70. Epub 2017 Apr 10.
    Department of Nephrology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
    Complement activation has a deep pathogenic influence in immunoglobulin (Ig)A nephropathy (IgAN). C3a and C5a, small cleavage fragments generated by complement activation, are key mediators of inflammation. The fragments exert broad proinflammatory effects by binding to specific receptors (C3aR and C5aR, respectively). Read More

    Cell-specific deletion of C1qa identifies microglia as the dominant source of C1q in mouse brain.
    J Neuroinflammation 2017 Mar 6;14(1):48. Epub 2017 Mar 6.
    Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, 92697, USA.
    Background: The complement cascade not only provides protection from infection but can also mediate destructive inflammation. Complement is also involved in elimination of neuronal synapses which is essential for proper development, but can be detrimental during aging and disease. C1q, required for several of these complement-mediated activities, is present in the neuropil, microglia, and a subset of interneurons in the brain. Read More

    Complement drives glucosylceramide accumulation and tissue inflammation in Gaucher disease.
    Nature 2017 03 22;543(7643):108-112. Epub 2017 Feb 22.
    Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
    Gaucher disease is caused by mutations in GBA1, which encodes the lysosomal enzyme glucocerebrosidase (GCase). GBA1 mutations drive extensive accumulation of glucosylceramide (GC) in multiple innate and adaptive immune cells in the spleen, liver, lung and bone marrow, often leading to chronic inflammation. The mechanisms that connect excess GC to tissue inflammation remain unknown. Read More

    Potential influences of complement factor H in autoimmune inflammatory and thrombotic disorders.
    Mol Immunol 2017 Apr 16;84:84-106. Epub 2017 Feb 16.
    Biosciences, College of Health and Life Sciences, Brunel University London, Uxbridge, UB8 3PH, United Kingdom. Electronic address:
    Complement system homeostasis is important for host self-protection and anti-microbial immune surveillance, and recent research indicates roles in tissue development and remodelling. Complement also appears to have several points of interaction with the blood coagulation system. Deficiency and altered function due to gene mutations and polymorphisms in complement effectors and regulators, including Factor H, have been associated with familial and sporadic autoimmune inflammatory - thrombotic disorders, in which autoantibodies play a part. Read More

    Genetic testing facilitates prepubertal diagnosis of congenital hypogonadotropic hypogonadism.
    Clin Genet 2017 Aug 30;92(2):213-216. Epub 2017 Mar 30.
    Endocrinology, Diabetology & Metabolism Service, Lausanne University Hospital, Lausanne, Switzerland.
    Neonatal micropenis and cryptorchidism raise the suspicion of congenital hypogonadotropic hypogonadism (CHH), a rare genetic disorder caused by gonadotropin-releasing hormone deficiency. Low plasma testosterone levels and low gonadotropins during minipuberty provide a clinical diagnostic clue, yet these tests are seldomly performed in general practice. We report a male neonate with no family history of reproductive disorders who was born with micropenis and cryptorchidism. Read More

    CD11b regulates the Treg/Th17 balance in murine arthritis via IL-6.
    Eur J Immunol 2017 Apr 13;47(4):637-645. Epub 2017 Mar 13.
    Department of Biochemistry CIIL, University of Lausanne, Epalinges, Switzerland.
    Th17 cells are often associated with autoimmunity and been shown to be increased in CD11b(-/-) mice. Here, we examined the role of CD11b in murine collagen-induced arthritis (CIA). C57BL/6 and CD11b(-/-) resistant mice were immunized with type II collagen. Read More

    What Kaplan-Meier survival curves don't tell us about CNS disease.
    J Neuroimmunol 2017 Jul 3;308:25-29. Epub 2017 Feb 3.
    Program in Cell and Molecular Biology, University of Pennsylvania, Philadelphia, PA, United States; Program in Blood Cell Development and Function, Fox Chase Cancer Center, Philadelphia, PA, United States. Electronic address:
    Central nervous system consequences of viral infections are rare, but when they do occur, they are often serious and clinically challenging to manage. Our awareness of the perils of neuroinvasion by viruses is growing: the recently appreciated impact of Ebola and Zika virus infections on CNS integrity, decreases in vaccination coverage for potentially neurotropic viruses such as measles, and increased neurovirulence of some influenza strains collectively highlight the need for a better understanding of the viral-neural interaction. Defining these interactions and how they result in neuropathogenesis is paramount for the development of better clinical strategies, especially given the limited treatment options that are available due to the unique physiology of the brain that limits migration of blood-borne molecules into the CNS parenchyma. Read More

    Skap2 is required for β2 integrin-mediated neutrophil recruitment and functions.
    J Exp Med 2017 Mar 9;214(3):851-874. Epub 2017 Feb 9.
    Department of Anesthesiology, Intensive Care, and Pain Medicine, University of Münster, 48149 Münster, Germany
    Integrin activation is required for neutrophil functions. Impaired integrin activation on neutrophils is the hallmark of leukocyte adhesion deficiency (LAD) syndrome in humans, characterized by impaired leukocyte recruitment and recurrent infections. The Src kinase-associated phosphoprotein 2 (Skap2) is involved in integrin functions in different leukocyte subtypes. Read More

    Activated β2 Integrins Restrict Neutrophil Recruitment during Murine Acute Pseudomonal Pneumonia.
    Am J Respir Cell Mol Biol 2017 May;56(5):620-627
    1 Division of Surgical Research, Department of Surgery, and.
    Rapid neutrophil recruitment is critical for the efficient clearance of bacterial pathogens from the lungs. Although β2 integrins and their activation are required for neutrophil recruitment from postcapillary venules of the systemic circulation into inflamed tissues, the involvement of integrins in neutrophil recruitment in response to respiratory infection varies among bacterial pathogens. For stimuli eliciting β2 integrin-dependent neutrophil influx, including Pseudomonas aeruginosa, it remains unclear whether the activation of β2 integrins is an essential step in this process. Read More

    C5 inhibition prevents renal failure in a mouse model of lethal C3 glomerulopathy.
    Kidney Int 2017 Jun 27;91(6):1386-1397. Epub 2017 Jan 27.
    Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. Electronic address:
    C3 glomerulopathy is a potentially life-threatening disease of the kidney caused by dysregulated alternative pathway complement activation. The specific complement mediator(s) responsible for kidney injury in C3 glomerulopathy are yet to be defined and no specific therapy is currently available. We previously developed a mouse model of lethal C3 glomerulopathy with factor H and properdin gene double mutations. Read More

    Divergent regulation of insulin-like growth factor binding protein genes in cultured Atlantic salmon myotubes under different models of catabolism and anabolism.
    Gen Comp Endocrinol 2017 Jun 19;247:53-65. Epub 2017 Jan 19.
    Institute of Biological and Environmental Sciences, University of Aberdeen, Tillydrone Avenue, Aberdeen AB24 2TZ, Scotland, United Kingdom. Electronic address:
    Much attention has been given to insulin-like growth factor (Igf) pathways that regulate the balance of skeletal muscle protein synthesis and breakdown in response to a range of extrinsic and intrinsic signals. However, we have a less complete understanding of how the same signals modulate muscle mass upstream of such signalling, through a family of functionally-diverse Igf-binding proteins (Igfbps) that modify the availability of Igfs to the cell receptor Igf1r. We exposed cultured myotubes from Atlantic salmon (Salmo salar L. Read More

    Cathepsin K Deficiency Ameliorates Systemic Lupus Erythematosus-like Manifestations in Fas(lpr) Mice.
    J Immunol 2017 Mar 16;198(5):1846-1854. Epub 2017 Jan 16.
    Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;
    Cysteinyl cathepsin K (CatK) is expressed in osteoclasts to mediate bone resorption, but is also inducible under inflammatory conditions. Fas(lpr) mice on a C57BL/6 background develop spontaneous systemic lupus erythematosus-like manifestations. Although normal mouse kidneys expressed negligible CatK, those from Fas(lpr) mice showed elevated CatK expression in the glomeruli and tubulointerstitial space. Read More

    The Zn(2+)-sensing receptor, ZnR/GPR39, upregulates colonocytic Cl(-) absorption, via basolateral KCC1, and reduces fluid loss.
    Biochim Biophys Acta 2017 Apr 16;1863(4):947-960. Epub 2017 Jan 16.
    Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel. Electronic address:
    Administration of zinc, as a complement to oral rehydration solutions, effectively diminishes duration and severity of diarrhea, but it is not known whether it merely fulfills a nutritional deficiency, or if zinc has a direct role of regulating solute absorption. We show that Zn(2+) acts via a specific receptor, ZnR/GPR39, to reduce fluid loss. Intestinal fluid secretion triggered by cholera toxin (CTx) was lower in WT mice compared to ZnR/GPR39 KO. Read More

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