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    2228 results match your criteria Complement Receptor Deficiency

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    Critical role for complement receptor C5aR2 in the pathogenesis of renal ischemia-reperfusion injury.
    FASEB J 2017 Apr 10. 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

    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 Mar 15. Epub 2017 Mar 15.
    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

    Complement drives glucosylceramide accumulation and tissue inflammation in Gaucher disease.
    Nature 2017 Mar 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 Feb 14. Epub 2017 Feb 14.
    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

    C5 inhibition prevents renal failure in a mouse model of lethal C3 glomerulopathy.
    Kidney Int 2017 Jan 27. 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

    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

    Androgenic effects of aqueous and methanolic extracts of Ficus asperifolia in male Wistar rats.
    BMC Complement Altern Med 2017 Jan 13;17(1):42. Epub 2017 Jan 13.
    Department of Animal Biology, Faculty of Science, Animal Physiology and Phytopharmacology Laboratory, University of Dschang, P.O. BOX 67, Dschang, Cameroon.
    Background: Androgen deficiency is a clinical syndrome resulting from the inability of the testes to produce physiological levels of testosterone due to a disturbance occurring at one or more levels of the hypothalamic-pituitary-testicular axis. The present study was undertaken to evaluate the androgenic properties of aqueous and methanolic extracts of Ficus asperifolia on normal and castrated immature rats.

    Methods: Normal rats were treated either per os with aqueous or methanolic extract of Ficus asperifolia (100 mg/kg or 500 mg/kg b. Read More

    Chronic lung disease in common variable immune deficiency (CVID): A pathophysiological role for microbial and non-B cell immune factors.
    Crit Rev Microbiol 2017 Jan 10:1-12. Epub 2017 Jan 10.
    a Halo Research Group, Queen's University Belfast , Belfast , United Kingdom.
    One of the most common and most severe forms of primary antibody deficiency encountered in the clinical setting is a heterogeneous group of syndromes termed common variable immune deficiency (CVID). This disorder is characterized by reduced immunoglobulin production and increased susceptibility to infection, particularly of the respiratory tract. Infection and subsequent immunological/inflammatory processes may contribute to the development of pulmonary complications such as bronchiectasis and interstitial lung disease. Read More

    The Role of Hippocampal Estradiol Receptor-α in a Perimenopausal Affective Disorders-Like Rat Model and Attenuating of Anxiety by Electroacupuncture.
    Evid Based Complement Alternat Med 2016 1;2016:4958312. Epub 2016 Dec 1.
    Department of Integrative Medicine and Neurobiology, State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Institute of Acupuncture Research (WHO Collaborating Center for Traditional Medicine), Institutes of Brain Science, Brain Science Collaborative Innovation Center, Fudan University, Shanghai 200032, China.
    Hormone replacement therapy is the principal treatment for perimenopausal affective disorders which can cause severe side effects. The present study compared the effects of electroacupuncture (EA) and estradiol treatment on perimenopausal affective disorders at the behavioral and cellular levels. In this randomized experimental in vivo study, adult female rats were divided into intact, ovariectomy, chronic unpredictable stress (CUS), and ovariectomy and CUS combination groups. Read More

    Complement peptide C3a stimulates neural plasticity after experimental brain ischaemia.
    Brain 2017 Feb 12;140(Pt 2):353-369. Epub 2016 Dec 12.
    Center for Brain Repair and Rehabilitation, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
    Ischaemic stroke induces endogenous repair processes that include proliferation and differentiation of neural stem cells and extensive rewiring of the remaining neural connections, yet about 50% of stroke survivors live with severe long-term disability. There is an unmet need for drug therapies to improve recovery by promoting brain plasticity in the subacute to chronic phase after ischaemic stroke. We previously showed that complement-derived peptide C3a regulates neural progenitor cell migration and differentiation in vitro and that C3a receptor signalling stimulates neurogenesis in unchallenged adult mice. Read More

    NLRP3 is Required for Complement-Mediated Caspase-1 and IL-1beta Activation in ICH.
    J Mol Neurosci 2017 Mar 8;61(3):385-395. Epub 2016 Dec 8.
    Department of Cerebrovascular Disease, The First Affiliated Hospital of Zunyi Medical College, No. 139, Dalian Avenue, Huichuan District, Zunyi, Guizhou, 563000, China.
    Complement-mediated inflammation plays a vital role in intracerebral hemorrhage (ICH), implicating pro-inflammatory factor interleukin-1beta (IL-1β) secretion. Brain samples and contralateral hemiencephalon were all collected and detected by Western blot. NLRP3 expression was located by dual immunofluorescence staining at 1, 3, and 5 days post-ICH. Read More

    Effect of SQW on the bladder function of mice lacking TRPV1.
    BMC Complement Altern Med 2016 Nov 15;16(1):465. Epub 2016 Nov 15.
    School of Fundamental Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
    Background: Suo Quan Wan (SQW) is an effective traditional Chinese prescription on treated lower urinary tract symptoms (LUTS), and has been proved have modulation effect on the expression of transient receptor potential vanilloid 1 (TRPV1) in accordance with the recovery of bladder function of overactive bladder rat. This study further investigated the mechanism of SQW modulated TRPV1 signaling and bladder function using TRPV1 knockout (KO) mice.

    Methods: Study was conducted using wild type and TRPV1 KO mice. Read More

    Myeloperoxidase deficiency enhances zymosan phagocytosis associated with up-regulation of surface expression of CD11b in mouse neutrophils.
    Free Radic Res 2016 Dec 2;50(12):1340-1349. Epub 2016 Nov 2.
    a Graduate School of Nanobioscience , Yokohama City University , Yokohama , Japan.
    Myeloperoxidase (MPO), a major component of neutrophils, catalyzes the production of hypochlorous acid (HOCl) from hydrogen peroxide and chloride anion. Phagocytosis is a critical event induced by neutrophils for host defense and inflammation. Interestingly, we found that MPO-deficient (MPO(-/-)) neutrophils engulfed larger amounts of zymosan than wild-type neutrophils. Read More

    Dietary choline deficiency and excess induced intestinal inflammation and alteration of intestinal tight junction protein transcription potentially by modulating NF-κB, STAT and p38 MAPK signaling molecules in juvenile Jian carp.
    Fish Shellfish Immunol 2016 Nov 28;58:462-473. Epub 2016 Sep 28.
    Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, 611130, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, 611130, China. Electronic address:
    This study investigated the effects of choline on intestinal mucosal immune and the possible mechanisms in fish by feeding juvenile Jian carp (Cyprinus carpio var. Jian) with graded levels of dietary choline (165-1820 mg/kg diet) for 65 days. The results firstly showed that choline deficiency induced inflammatory infiltration in the proximal intestine (PI), mid intestine (MI) and distal intestine (DI) of fish. Read More

    Novelties in the Diagnosis and Treatment of Angioedema.
    J Investig Allergol Clin Immunol 2016 ;26(4):212-21; quiz two pages after page 221
    Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, ASST Fatebenefratelli Sacco, Milano, Italy.
    Angioedema is defined as local, noninflammatory, self-limiting edema that is circumscribed owing to increased leakage of plasma from the capillaries located in the deep layers of the skin and the mucosae. Two mediators, histamine and bradykinin, account for most cases of angioedema. Angioedema can occur with wheals as a manifestation of urticaria, and this form is frequently allergic. Read More

    HAE Pathophysiology and Underlying Mechanisms.
    Clin Rev Allergy Immunol 2016 Oct;51(2):216-29
    Department of Medicine, University of California, 9500 Gilman Dr., Mail code 0732, La Jolla, CA, 92093-0732, USA.
    Remarkable progress in understanding the pathophysiology and underlying mechanisms of hereditary angioedema has led to the development of effective treatment for this disorder. Progress in three separate areas has catalyzed our understanding of hereditary angioedema. The first is the recognition that HAE type I and type II result from a deficiency in the plasma level of functional C1 inhibitor. Read More

    Bidirectional Crosstalk between C5a Receptors and the NLRP3 Inflammasome in Macrophages and Monocytes.
    Mediators Inflamm 2016 7;2016:1340156. Epub 2016 Jun 7.
    Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
    C5a is an inflammatory mediator generated by complement activation that positively regulates various arms of immune defense, including Toll-like receptor 4 (TLR4) signaling. The NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome is activated by pathogen products and cellular/tissue damage products and is a major contributor of IL-1β. In this study, we investigate whether C5a modulates lipopolysaccharide- (LPS-) induced NLRP3 inflammasome activation in myeloid cells. Read More

    A Mouse Model for Dietary Xenosialitis: ANTIBODIES TO XENOGLYCAN CAN REDUCE FERTILITY.
    J Biol Chem 2016 Aug 5;291(35):18222-31. Epub 2016 Jul 5.
    the Glycobiology Research and Training Center and Department of Pathology,
    Humans can incorporate the xenoglycan N-glycolylneuraminic acid (Neu5Gc) from the diet into reproductive tissues and secretions. Most humans also have circulating antibodies specific for this dietary xenoglycan. The potential for inflammation induced by incorporated Neu5Gc and circulating anti-Neu5Gc antibodies, termed xenosialitis, has been discussed as a factor influencing several human diseases. Read More

    Complement Component C1q Programs a Pro-Efferocytic Phenotype while Limiting TNFα Production in Primary Mouse and Human Macrophages.
    Front Immunol 2016 15;7:230. Epub 2016 Jun 15.
    Department of Microbiology and Immunology, Des Moines University , Des Moines, IA , USA.
    Deficiency in complement component C1q is associated with an inability to clear apoptotic cells (efferocytosis) and aberrant inflammation in lupus, and identification of the pathways involved in these processes should reveal important regulatory mechanisms in lupus and other autoimmune or inflammatory diseases. In this study, C1q-dependent regulation of TNFα/IL-6 expression and efferocytosis was investigated using primary mouse bone marrow-derived macrophages and human monocyte-derived macrophages. C1q downregulated LPS-dependent TNFα production in mouse and human macrophages. Read More

    The collectins CL-L1, CL-K1 and CL-P1, and their roles in complement and innate immunity.
    Immunobiology 2016 Oct 2;221(10):1058-67. Epub 2016 Jun 2.
    Department of Microbiology and Immunochemistry, Asahikawa Medical University, Asahikawa, Japan. Electronic address:
    Both the complement system and collectins play important roles in our innate immune system. The collectins, which are characterized by their inclusion of a collagen-like region and a calcium-dependent carbohydrate recognition domain, are pattern recognition molecules and include the well characterized proteins mannan-binding lectin (MBL) and the surfactant proteins SP-A/-D. Collectin liver 1 (CL-L1), collectin kidney 1 (CL-K1) and collectin placenta 1 (CL-P1) are the most recently discovered collectins. Read More

    A complement-microglial axis drives synapse loss during virus-induced memory impairment.
    Nature 2016 06;534(7608):538-43
    Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA.
    Over 50% of patients who survive neuroinvasive infection with West Nile virus (WNV) exhibit chronic cognitive sequelae. Although thousands of cases of WNV-mediated memory dysfunction accrue annually, the mechanisms responsible for these impairments are unknown. The classical complement cascade, a key component of innate immune pathogen defence, mediates synaptic pruning by microglia during early postnatal development. Read More

    Complement and Antibody-mediated Enhancement of Red Blood Cell Invasion and Growth of Malaria Parasites.
    EBioMedicine 2016 Jul 14;9:207-16. Epub 2016 May 14.
    Department of Microbiology and Immunology, Pennsylvania State University, College of Medicine, 500 University Drive, Hershey, PA 17033, United States; Department of Medicine, Division of Infectious Diseases and Epidemiology, Pennsylvania State University, College of Medicine, 500 University Drive, Hershey, PA 17033, United States. Electronic address:
    Plasmodium falciparum malaria is a deadly pathogen. The invasion of red blood cells (RBCs) by merozoites is a target for vaccine development. Although anti-merozoite antibodies can block invasion in vitro, there is no efficacy in vivo. Read More

    FHR3 Blocks C3d-Mediated Coactivation of Human B Cells.
    J Immunol 2016 Jul 8;197(2):620-9. Epub 2016 Jun 8.
    Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, 07745 Jena, Germany;
    The autoimmune renal disease deficient for complement factor H-related (CFHR) genes and autoantibody-positive form of hemolytic uremic syndrome is characterized by the presence of autoantibodies specific for the central complement regulator, factor H, combined with a homozygous deficiency, mostly in CFHR3 and CFHR1 Because FHR3 and FHR1 bind to C3d and inactivated C3b, which are ligands for complement receptor type 2 (CR2/CD21), the aim of the current study was to examine whether FHR3-C3d or FHR1-C3d complexes modulate B cell activation. Laser-scanning microscopy and automated image-based analysis showed that FHR3, but not FHR1 or factor H, blocked B cell activation by the BCR coreceptor complex (CD19/CD21/CD81). FHR3 bound to C3d, thereby inhibiting the interaction between C3d and CD21 and preventing colocalization of the coreceptor complex with the BCR. Read More

    Vitamin D3: A Role in Dopamine Circuit Regulation, Diet-Induced Obesity, and Drug Consumption.
    eNeuro 2016 Mar-Apr;3(2). Epub 2016 May 19.
    Department of Psychiatry, Yale University School of Medicine , New Haven, Connecticut 06519.
    The influence of micronutrients on dopamine systems is not well defined. Using mice, we show a potential role for reduced dietary vitamin D3 (cholecalciferol) in promoting diet-induced obesity (DIO), food intake, and drug consumption while on a high fat diet. To complement these deficiency studies, treatments with exogenous fully active vitamin D3 (calcitriol, 10 µg/kg, i. Read More

    Angioedema attacks in patients with hereditary angioedema: Local manifestations of a systemic activation process.
    J Allergy Clin Immunol 2016 Aug 28;138(2):359-66. Epub 2016 May 28.
    Laboratory for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address:
    Hereditary angioedema (HAE) caused by a deficiency of functional C1-inhibitor (C1INH) becomes clinically manifest as attacks of angioedema. C1INH is the main inhibitor of the contact system. Poor control of a local activation process of this system at the site of the attack is believed to lead to the formation of bradykinin (BK), which increases local vasopermeability and mediates angioedema on interaction with BK receptor 2 on the endothelium. Read More

    Characterization of the Regulation of CD46 RNA Alternative Splicing.
    J Biol Chem 2016 Jul 12;291(27):14311-23. Epub 2016 May 12.
    From the School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore
    Here we present a detailed analysis of the alternative splicing regulation of human CD46, which generates different isoforms with distinct functions. CD46 is a ubiquitous membrane protein that protects host cells from complement and plays other roles in immunity, autophagy, and cell adhesion. CD46 deficiency causes an autoimmune disorder, and this protein is also involved in pathogen infection and cancer. Read More

    The combination of Artemisia princeps Pamp, Leonurus japonicas Houtt, and Gardenia jasminoides Ellis fruit attenuates the exacerbation of energy, lipid, and glucose by increasing hepatic PGC-1α expression in estrogen-deficient rats.
    BMC Complement Altern Med 2016 May 23;16:137. Epub 2016 May 23.
    Department of Food and Nutrition, Obesity/Diabetes Center, Hoseo University, Asan, Korea.
    Background: Artemisia princeps Pamp (APP), Leonurus japonicas Houtt (LJH), and Gardenia jasminoides Ellis fruit (GJE) have been traditionally used in East Asia to treat women's diseases related to reproductive system. They may attenuate the deterioration of energy, lipid, glucose and bone metabolism by estrogen deficiency. The present study explored the combination of APP, LJH, and GJE to overcome the symptoms of estrogen deficiency and the mechanism was explored. Read More

    A Decade of Change: Recent Developments in Pharmacotherapy of Hereditary Angioedema (HAE).
    Clin Rev Allergy Immunol 2016 Oct;51(2):183-92
    Department of Dermatology, Johannes Gutenberg University, Langenbeckstr 1, 55131, Mainz, Germany.
    Hereditary angioedema (HAE) due to C1 esterase inhibitor (C1-INH) deficiency (HAE-C1-INH) is a rare but medically significant disease that can be associated with considerable morbidity and mortality. Research into the pathogenesis of HAE-C1-INH has expanded greatly in the last six decades and has led to new clinical trials with novel therapeutic agents and treatment strategies. Mechanisms of pharmacotherapy include (a) supplementing C1-INH, the missing serine-protease inhibitor in HAE; (b) inhibiting the activation of the contact system and the uncontrolled release of proteases in the kallikrein-kinin system, by blocking the production/function of its components; (c) inhibiting the fibrinolytic system by blocking the production/function of its components; and (d) inhibiting the function of bradykinin at the endothelial level. Read More

    The Complement C3a Receptor Contributes to Melanoma Tumorigenesis by Inhibiting Neutrophil and CD4+ T Cell Responses.
    J Immunol 2016 Jun 20;196(11):4783-92. Epub 2016 Apr 20.
    Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland 4072, Australia;
    The complement peptide C3a is a key component of the innate immune system and a major fragment produced following complement activation. We used a murine model of melanoma (B16-F0) to identify a hitherto unknown role for C3a-C3aR signaling in promoting tumor growth. The results show that the development and growth of B16-F0 melanomas is retarded in mice lacking C3aR, whereas growth of established melanomas can be arrested by C3aR antagonism. Read More

    Phospholipase A2 Receptor-Related Membranous Nephropathy and Mannan-Binding Lectin Deficiency.
    J Am Soc Nephrol 2016 Dec 6;27(12):3539-3544. Epub 2016 May 6.
    Laboratoire d'Immunologie, Pôle de Biologie, Centre Hospitalier Universitalier de Grenoble, Grenoble, France.
    Most patients with idiopathic membranous nephropathy (IMN) have IgG4 autoantibodies against phospholipase A2 receptor (PLA2R). C3 and C5b-9 are found in immune deposits of IMN kidney biopsy specimens, but the pathway of complement activation in IMN remains elusive. We report the case of a patient who developed IMN with intense staining for PLA2R, IgG4, C3, C5b-9, factor B, and properdin and very weak staining for C1q, C4d, and IgG1. Read More

    Ablating the aryl hydrocarbon receptor (AhR) in CD11c+ cells perturbs intestinal epithelium development and intestinal immunity.
    Sci Rep 2016 Apr 12;6:23820. Epub 2016 Apr 12.
    Singapore Centre on Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, 60 Nanyang Drive, Singapore 637551.
    Diet and microbiome derived indole derivatives are known to activate the ligand induced transcription factor, the Aryl hydrocarbon Receptor (AhR). While the current understanding of AhR biology has confirmed its role in mucosal lymphocytes, its function in intestinal antigen presenting cells (APCs) is poorly understood. Here, we report that Cre-mediated deletion of AhR in CD11c-expressing cells in C57/BL6 mice is associated with altered intestinal epithelial morphogenesis in vivo. Read More

    Yarrowia lipolytica AAL genes are involved in peroxisomal fatty acid activation.
    Biochim Biophys Acta 2016 Jul 9;1861(7):555-65. Epub 2016 Apr 9.
    Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, 78350, Jouy-en-Josas, France. Electronic address:
    In yeast, β-oxidation of fatty acids (FAs) essentially takes place in peroxisomes, and FA activation must precede FA oxidation. In Saccharomyces cerevisiae, a single fatty-acyl–CoA-synthetase, ScFaa2p, mediates peroxisomal FA activation. We have previously shown that this reaction also exists in the oleaginous yeast Yarrowia lipolytica; however, the protein involved in this process remains unknown. Read More

    The complement receptor C5aR1 contributes to renal damage but protects the heart in angiotensin II-induced hypertension.
    Am J Physiol Renal Physiol 2016 Jun 6;310(11):F1356-65. Epub 2016 Apr 6.
    Department of Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany;
    Adaptive and innate immune responses contribute to hypertension and hypertensive end-organ damage. Here, we determined the role of anaphylatoxin C5a, a major inflammatory effector of the innate immune system that is generated in response to complement activation, in hypertensive end-organ damage. For this purpose, we assessed the phenotype of C5a receptor 1 (C5aR1)-deficient mice in ANG II-induced renal and cardiac injury. Read More

    A Transmembrane Polymorphism of Fcγ Receptor IIb Is Associated with Kidney Deficiency Syndrome in Rheumatoid Arthritis.
    Evid Based Complement Alternat Med 2016 8;2016:3214657. Epub 2016 Mar 8.
    Division of Rheumatology and Clinical Immunology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China.
    Objective. The purpose is to investigate the role of kidney deficiency and the association between kidney deficiency and a polymorphism FcγRIIb 695T>C coding for nonsynonymous substitution IIe232Thr (I232T) in rheumatoid arthritis (RA). Methods. Read More

    Linking CD11b (+) Dendritic Cells and Natural Killer T Cells to Plaque Inflammation in Atherosclerosis.
    Mediators Inflamm 2016 9;2016:6467375. Epub 2016 Mar 9.
    Laboratory of Physiopharmacology, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, 2610 Antwerp, Belgium.
    Atherosclerosis remains the leading cause of death and disability in our Western society. To investigate whether the dynamics of leukocyte (sub)populations could be predictive for plaque inflammation during atherosclerosis, we analyzed innate and adaptive immune cell distributions in blood, plaques, and lymphoid tissue reservoirs in apolipoprotein E-deficient (ApoE(-/-)) mice and in blood and plaques from patients undergoing endarterectomy. Firstly, there was predominance of the CD11b(+) conventional dendritic cell (cDC) subset in the plaque. Read More

    Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO.hCD46.hTBM pig-to-primate cardiac xenograft.
    Nat Commun 2016 Apr 5;7:11138. Epub 2016 Apr 5.
    Cardiothoracic Surgery Research Program, NHLBI, NIH, Bethesda, Maryland 20892, USA.
    Preventing xenograft rejection is one of the greatest challenges of transplantation medicine. Here, we describe a reproducible, long-term survival of cardiac xenografts from alpha 1-3 galactosyltransferase gene knockout pigs, which express human complement regulatory protein CD46 and human thrombomodulin (GTKO.hCD46. Read More

    Targeted Deletion of Vesicular GABA Transporter from Retinal Horizontal Cells Eliminates Feedback Modulation of Photoreceptor Calcium Channels.
    eNeuro 2016 Mar-Apr;3(2). Epub 2016 Mar 10.
    Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095; Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, California 90073; Jules Stein Eye Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095.
    The cellular mechanisms underlying feedback signaling from horizontal cells to photoreceptors, which are important for the formation of receptive field surrounds of early visual neurons, remain unsettled. Mammalian horizontal cells express a complement of synaptic proteins that are necessary and sufficient for calcium-dependent exocytosis of inhibitory neurotransmitters at their contacts with photoreceptor terminals, suggesting that they are capable of releasing GABA via vesicular release. To test whether horizontal cell vesicular release is involved in feedback signaling, we perturbed inhibitory neurotransmission in these cells by targeted deletion of the vesicular GABA transporter (VGAT), the protein responsible for the uptake of inhibitory transmitter by synaptic vesicles. Read More

    IVIG in autoimmune disease - Potential next generation biologics.
    Autoimmun Rev 2016 Aug 25;15(8):781-5. Epub 2016 Mar 25.
    CSL Behring AG, Research, Switzerland.
    Polyclonal plasma-derived IgG is a mainstay therapeutic of immunodeficiency disorders as well as of various inflammatory autoimmune diseases. In immunodeficiency the primary function of IVIG/SCIG is to replace missing antibody specificities, consequently a diverse Fab-based repertoire is critical for efficacy. Attempts to capture the Ig repertoire and express it as a recombinant IVIG product are currently ongoing. Read More

    Hereditary and acquired C1-inhibitor-dependent angioedema: from pathophysiology to treatment.
    Ann Med 2016 26;48(4):256-67. Epub 2016 Mar 26.
    c Department of Internal Medicine , Academic Medical Center, University of Amsterdam , The Netherlands.
    Uncontrolled generation of bradykinin (BK) due to insufficient levels of protease inhibitors controlling contact phase (CP) activation, increased activity of CP proteins, and/or inadequate degradation of BK into inactive peptides increases vascular permeability via BK-receptor 2 (BKR2) and results in subcutaneous and submucosal edema formation. Hereditary and acquired angioedema due to C1-inhibitor deficiency (C1-INH-HAE and -AAE) are diseases characterized by serious and potentially fatal attacks of subcutaneous and submucosal edemas of upper airways, facial structures, abdomen, and extremities, due to inadequate control of BK generation. A decreased activity of C1-inhibitor is the hallmark of C1-INH-HAE (types 1 and 2) due to a mutation in the C1-inhibitor gene, whereas the deficiency in C1-inhibitor in C1-INH-AAE is the result of autoimmune phenomena. Read More

    Neural Androgen Receptors Modulate Gene Expression and Social Recognition But Not Social Investigation.
    Front Behav Neurosci 2016 16;10:41. Epub 2016 Mar 16.
    Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg Gothenburg, Sweden.
    The role of sex and androgen receptors (ARs) for social preference and social memory is rather unknown. In this study of mice we compared males, females and males lacking ARs specifically in the nervous system, AR(NesDel), with respect to social preference, assessed with the three-chambered apparatus test, and social recognition, assessed with the social discrimination procedure. In the social discrimination test we also evaluated the tentative importance of the sex of the stimulus animal. Read More

    C1q propagates microglial activation and neurodegeneration in the visual axis following retinal ischemia/reperfusion injury.
    Mol Neurodegener 2016 Mar 24;11:24. Epub 2016 Mar 24.
    North Texas Eye Research Institute, University of North Texas Health Science Center, CBH-441, 3500 Camp Bowie Boulevard, Fort Worth, TX, 76107, USA.
    Background: C1q represents the initiating protein of the classical complement cascade, however recent findings indicate pathway independent roles such as developmental pruning of retinal ganglion cell (RGC) axons. Furthermore, chronic neuroinflammation, including increased expression of C1q and activation of microglia and astrocytes, appears to be a common finding among many neurodegenerative disease models. Here we compare the effects of a retinal ischemia/reperfusion (I/R) injury on glial activation and neurodegeneration in wild type (WT) and C1qa-deficient mice in the retina and superior colliculus (SC). Read More

    Prophylaxis in hereditary angioedema (HAE) with C1 inhibitor deficiency.
    J Dtsch Dermatol Ges 2016 Mar;14(3):266-75
    Department of Dermatology and Allergy, Allergie-Centrum-Charité, Charité - Universitätsmedizin, Berlin, Germany.
    Hereditary angioedema (HAE) is a rare congenital disorder characterized by recurrent episodes of subcutaneous or submucosal edema. Laryngeal manifestations can be life-threatening. In the majority of cases, the disease can be adequately treated with an on-demand approach--in some cases, however, short- or long-term prophylaxis is indicated. Read More

    Serological and Genetic Evidence for Altered Complement System Functionality in Systemic Lupus Erythematosus: Findings of the GAPAID Consortium.
    PLoS One 2016 7;11(3):e0150685. Epub 2016 Mar 7.
    Department of Rheumatology and Immunology, Clinic Center, University of Pécs, Pécs, Hungary.
    Systemic lupus erythematosus is a chronic autoimmune disease with multifactorial ethiopathogenesis. The complement system is involved in both the early and late stages of disease development and organ damage. To better understand autoantibody mediated complement consumption we examined ex vivo immune complex formation on autoantigen arrays. Read More

    Complement receptor 3 mediates renal protection in experimental C3 glomerulopathy.
    Kidney Int 2016 Apr 3;89(4):823-32. Epub 2016 Feb 3.
    Centre for Complement and Inflammation Research, Imperial College, London, UK. Electronic address:
    C3 glomerulopathy is a complement-mediated renal disease that is frequently associated with abnormalities in regulation of the complement alternative pathway. Mice with deficiency of factor H (Cfh(-/-)), a negative alternative pathway regulator, are an established experimental model of C3 glomerulopathy in which complement C3 fragments including iC3b accumulate along the glomerular basement membrane. Here we show that deficiency of complement receptor 3 (CR3), the main receptor for iC3b, enhances the severity of spontaneous renal disease in Cfh(-/-) mice. Read More

    Early Components of the Complement Classical Activation Pathway in Human Systemic Autoimmune Diseases.
    Front Immunol 2016 15;7:36. Epub 2016 Feb 15.
    Center for Molecular and Human Genetics, Division of Pediatric Rheumatology, Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University , Columbus, OH , USA.
    The complement system consists of effector proteins, regulators, and receptors that participate in host defense against pathogens. Activation of the complement system, via the classical pathway (CP), has long been recognized in immune complex-mediated tissue injury, most notably systemic lupus erythematosus (SLE). Paradoxically, a complete deficiency of an early component of the CP, as evidenced by homozygous genetic deficiencies reported in human, are strongly associated with the risk of developing SLE or a lupus-like disease. Read More

    Peripheral Lymphoid Volume Expansion and Maintenance Are Controlled by Gut Microbiota via RALDH+ Dendritic Cells.
    Immunity 2016 Feb;44(2):330-42
    Institute for Immunology, Department of Basic Medical Sciences, School of Medicine, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China; Department of Microbiology, Immunology and Infectious Diseases and Snyder Institute for Chronic Diseases, University of Calgary Calgary, AB T2N 1N4, Canada. Electronic address:
    Lymphocyte homing to draining lymph nodes is critical for the initiation of immune responses. Secondary lymphoid organs of germ-free mice are underdeveloped. How gut commensal microbes remotely regulate cellularity and volume of secondary lymphoid organs remains unknown. Read More

    Components of the lectin pathway of complement activation in paediatric patients of intensive care units.
    Immunobiology 2016 May 15;221(5):657-69. Epub 2016 Jan 15.
    Laboratory of Immunobiology of Infections, Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232 Lodz, Poland. Electronic address:
    Infections are a major cause of childhood mortality. We investigated components of the lectin pathway of complement activation in the context of sepsis at both genetic and protein levels in neonates, infants and older children. Major components of the lectin pathway and two genes for Toll-like receptors were studied in 87 neonates with confirmed sepsis and compared with 40 babies with infections who did not develop sepsis (disease controls) and 273 infection-free neonatal controls. Read More

    Complement component C3a plays a critical role in endothelial activation and leukocyte recruitment into the brain.
    J Neuroinflammation 2016 Jan 28;13:23. Epub 2016 Jan 28.
    Department of Immunology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, JS, 210029, China.
    Background: The complement system is becoming increasingly recognized as a key participant in many neurodegenerative diseases of the brain. Complement-deficient animals exhibit reduced neuroinflammation.

    Methods: In the present study, we administered intracerebroventricularly lipopolysaccharide (LPS) to mimic local infection of the brain and investigated the role of key complement component C3 in brain vasculature endothelial activation and leukocyte recruitment. Read More

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