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

Biochim Biophys Acta 2017 Jun 7. 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Crit Rev Microbiol 2017 Aug 10;43(4):508-519. 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

Am J Physiol Renal Physiol 2017 Mar 4;312(3):F516-F532. Epub 2017 Jan 4.

Division of Nephrology, Center for Immunity, Inflammation, and Regenerative Medicine, University of Virginia, Charlottesville, Virginia;

We have examined the pathogenic role of increased complement expression and activation during kidney fibrosis. Here, we show that PDGFRβ-positive pericytes isolated from mice subjected to obstructive or folic acid injury secrete C1q. This was associated with increased production of proinflammatory cytokines, extracellular matrix components, collagens, and increased Wnt3a-mediated activation of Wnt/β-catenin signaling, which are hallmarks of myofibroblast activation. Read More

Transplantation 2017 Apr;101(4):e75-e85

1 Department of Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China. 2 Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC. 3 Department of Surgery, Division of Transplantation, Lee Patterson Allen Transplant Immunobiology Laboratory, Medical University of South Carolina, Charleston, SC. 4 South Carolina Investigators in Transplantation (SCIT), Medical University of South Carolina, Charleston, SC. 5 Ralph H. Johnson Veteran Affairs Medical Center, Charleston, SC.

Background: Recipients of vascularized composite allografts require aggressive and lifelong immunosuppression, and because the surgery is usually performed in nonlife-threatening situations, the development of strategies to minimize immunosuppression is especially pertinent for this procedure. We investigated how complement affects acute graft injury, alloimmunity, and immunosuppressive therapy.

Methods: Vascularized composite allografts were transplanted from Balb/C to C57BL/6 mice that were complement deficient (C3 or double C3a Receptor (R)/C5aR), or treated with a targeted complement inhibitor (CR2-Crry). Read More

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

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

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

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

Eur J Immunol 2016 Nov 26;46(11):2614-2628. Epub 2016 Sep 26.

Laboratory of Cellular and Molecular Immunology, GIGA-I3, GIGA-Research Center and Faculty of Veterinary Medicine, University of Liege, Liege, Belgium.

Very few transcription factors have been identified that are required by antigen-presenting cells (APCs) to induce T helper type 2 (Th2) responses. Because lung CD11b(+) conventional dendritic cells (CD11b(+) cDCs) are responsible for priming Th2 responses in house-dust mite (HDM)-induced airway allergy, we used them as a model to identify transcriptional events regulating the pro-Th2 activity of cDCs. Transcriptomic profiling of lung CD11b(+) cDCs exposed to HDM in vivo revealed first that HDM triggers an antiviral defence-like response, and second that the majority of HDM-induced transcriptional changes depend on the transcription factor Interferon Response Factor-3 (Irf3). Read More

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

Infect Immun 2017 Jan 29;85(1). Epub 2016 Dec 29.

Department of Molecular Cardiology, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA

Integrins αMβ2 and αXβ2 are homologous adhesive receptors that are expressed on many of the same leukocyte populations and bind many of the same ligands. Although αMβ2 was extensively characterized and implicated in leukocyte inflammatory and immune functions, the roles of αXβ2 remain largely obscure. Here, we tested the ability of mice deficient in integrin αMβ2 or αXβ2 to deal with opportunistic infections and the capacity of cells derived from these animals to execute inflammatory functions. Read More

Am J Respir Cell Mol Biol 2016 Nov;55(5):657-666

1 Division of Respiratory Diseases, Boston Children's Hospital, Boston, Massachusetts.

LPS-induced lung injury in the mouse is one of the most robust experimental models used for studies of acute lung injury (ALI) and acute respiratory distress syndrome in humans. Prior clinical and experimental studies support an important role for complement activation, particularly production of C5a, in the pathophysiology of human ALI/acute respiratory distress syndrome. In the mouse model, however, the precise role of C5a and its receptors is unclear. Read More

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

PLoS One 2016 6;11(10):e0162532. Epub 2016 Oct 6.

Department of Molecular Pharmacology, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Kanagawa, Japan.

Lymphangiogenesis plays an important role in homeostasis, metabolism, and immunity, and also occurs during wound-healing. Here, we examined the roles of prostaglandin E2 (PGE2) receptor (EP) signaling in enhancement of lymphangiogenesis in wound healing processes. The hole-punch was made in the ears of male C57BL/6 mice using a metal ear punch. Read More

Diabetes 2016 Oct;65(10):2888-99

Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

Type 2 diabetes and cardiovascular disease are complex disorders involving metabolic and inflammatory mechanisms. Here we investigated whether sCD93, a group XIV c-type lectin of the endosialin family, plays a role in metabolic dysregulation or carotid intima-media thickness (IMT). Although no association was observed between sCD93 and IMT, sCD93 levels were significantly lower in subjects with type 2 diabetes (n = 901, mean ± SD 156. Read More

Exp Eye Res 2016 Oct 23;151:122-33. Epub 2016 Aug 23.

F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, USA. Electronic address:

Iron accumulation in the retina is associated with the development of age-related macular degeneration (AMD). IV iron is a common method to treat iron deficiency anemia in adults, and its retinal manifestations have not hitherto been identified. To assess whether IV iron formulations can be retina-toxic, we generated a mouse model for iron-induced retinal damage. Read More

J Neurosci 2016 Aug;36(33):8653-67

Department of Neuroscience and Regenerative Medicine,

Unlabelled: Recent evidence implicates exosomes in the aggregation of Aβ and spreading of tau in Alzheimer's disease. In neural cells, exosome formation can be blocked by inhibition or silencing of neutral sphingomyelinase-2 (nSMase2). We generated genetically nSMase2-deficient 5XFAD mice (fro;5XFAD) to assess AD-related pathology in a mouse model with consistently reduced ceramide generation. Read More

J Immunol 2016 Sep 12;197(6):2353-61. Epub 2016 Aug 12.

Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109;

There is accumulating evidence during sepsis that cardiomyocyte (CM) homeostasis is compromised, resulting in cardiac dysfunction. An important role for complement in these outcomes is now demonstrated. Addition of C5a to electrically paced CMs caused prolonged elevations of intracellular Ca(2+) concentrations during diastole, together with the appearance of spontaneous Ca(2+) transients. Read More

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

J Allergy Clin Immunol 2017 Jan 14;139(1):220-231.e8. Epub 2016 Jun 14.

Center for Chronic Immunodeficiency, University Medical Center and University of Freiburg, Freiburg, Germany. Electronic address:

Background: Most patients with common variable immunodeficiency (CVID) present with severely reduced switched memory B-cell counts, and some display an increase of CD21(low) B-cell counts (CVID 21low), whereas others do not (CVID 21norm). Altered B-cell receptor (BCR) signaling might contribute to the defective memory formation observed in patients with CVID.

Objective: We sought to investigate canonical nuclear factor of κ light chain (NF-κB) signaling in B cells from patients with CVID as a central pathway in B-cell differentiation. Read More

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

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

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

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

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

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

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

Am J Pathol 2016 Aug 14;186(8):2105-16. Epub 2016 Jun 14.

Center for Metabolic and Vascular Biology, School of Life Sciences, Arizona State University, Tempe, Arizona. Electronic address:

The subfamily of β2 integrins is implicated in macrophage fusion, a hallmark of chronic inflammation. Among β2 family members, integrin Mac-1 (αMβ2, CD11b/CD18) is abundantly expressed on monocyte/macrophages and mediates critical adhesive reactions of these cells. However, the role of Mac-1 in macrophage fusion leading to the formation of multinucleated giant cells remains unclear. Read More

Am J Pathol 2016 Aug 11;186(8):2088-104. Epub 2016 Jun 11.

Department of Ophthalmology, Jones Eye Institute, Pat and Willard Walker Eye Research Center, University of Arkansas for Medical Sciences, Little Rock, Arkansas; Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas. Electronic address:

In the mouse, membrane cofactor protein (CD46), a key regulator of the alternative pathway of the complement system, is only expressed in the eye and on the inner acrosomal membrane of spermatozoa. We noted that although Cd46(-/-) mice have normal systemic alternative pathway activating ability, lack of CD46 leads to dysregulated complement activation in the eye, as evidenced by increased deposition of C5b-9 in the retinal pigment epithelium (RPE) and choroid. A knockout of CD46 induced the following cardinal features of human dry age-related macular degeneration (AMD) in 12-month-old male and female mice: accumulation of autofluorescent material in and hypertrophy of the RPE, dense deposits in and thickening of Bruch's membrane, loss of photoreceptors, cells in subretinal space, and a reduction of choroidal vessels. Read More

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

Arthritis Rheumatol 2016 Dec;68(12):2917-2928

University of Florida, Gainesville.

Objective: In vitro studies suggest that the type I interferon (IFN) signature seen in most lupus patients results from Fcγ receptor-mediated uptake of nucleic acid-containing immune complexes by plasmacytoid dendritic cells and engagement of endosomal Toll-like receptors. The aim of this study was to reexamine the pathogenesis of the IFN signature in vivo.

Methods: Lupus was induced in mice by injecting pristane. Read More

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