Landscape of Innate Immune System Transcriptome and Acute T-Cell
Total Page:16
File Type:pdf, Size:1020Kb

Load more
Recommended publications
-
Analysis of Gene–Environment Interactions in Postnatal
– Analysis of gene environment interactions in postnatal INAUGURAL ARTICLE development of the mammalian intestine Seth Rakoff-Nahouma,b,c,1, Yong Kongd, Steven H. Kleinsteine, Sathish Subramanianf, Philip P. Ahernf, Jeffrey I. Gordonf, and Ruslan Medzhitova,b,1 aHoward Hughes Medical Institute, bDepartment of Immunobiology, dDepartment of Molecular Biophysics and Biochemistry, W. M. Keck Foundation Biotechnology Resource Laboratory, and eInterdepartmental Program in Computational Biology and Bioinformatics and Department of Pathology, Yale University School of Medicine, New Haven, CT 06510; fCenter for Genome Sciences and Systems Biology, Washington University School of Medicine in St. Louis, St. Louis, MO 63108; and cDivision of Infectious Diseases, Department of Medicine, Boston Children’s Hospital and Harvard Medical School, Boston, MA 02115 This contribution is part of the special series of Inaugural Articles by members of the National Academy of Sciences elected in 2010. Contributed by Ruslan Medzhitov, December 31, 2014 (sent for review December 25, 2014; reviewed by Alexander V. Chervonsky and Alexander Y. Rudensky) Unlike mammalian embryogenesis, which takes place in the relatively immediately after birth, the intestine is exposed to mother’s milk predictable and stable environment of the uterus, postnatal develop- and undergoes initial colonization with microorganisms. Second, ment can be affected by a multitude of highly variable environmental after weaning, the intestinal tract becomes exposed to solid foods factors, including diet, exposure to noxious substances, and micro- and is no longer exposed to mother’s milk components, the host organisms. Microbial colonization of the intestine is thought to play a immune system matures, and the microbiota shifts. particularly important role in postnatal development of the gastroin- Although it is widely recognized that these transitions have testinal, metabolic, and immune systems. -
Role of Nlrs in the Regulation of Type I Interferon Signaling, Host Defense and Tolerance to Inflammation
International Journal of Molecular Sciences Review Role of NLRs in the Regulation of Type I Interferon Signaling, Host Defense and Tolerance to Inflammation Ioannis Kienes 1, Tanja Weidl 1, Nora Mirza 1, Mathias Chamaillard 2 and Thomas A. Kufer 1,* 1 Department of Immunology, Institute for Nutritional Medicine, University of Hohenheim, 70599 Stuttgart, Germany; [email protected] (I.K.); [email protected] (T.W.); [email protected] (N.M.) 2 University of Lille, Inserm, U1003, F-59000 Lille, France; [email protected] * Correspondence: [email protected] Abstract: Type I interferon signaling contributes to the development of innate and adaptive immune responses to either viruses, fungi, or bacteria. However, amplitude and timing of the interferon response is of utmost importance for preventing an underwhelming outcome, or tissue damage. While several pathogens evolved strategies for disturbing the quality of interferon signaling, there is growing evidence that this pathway can be regulated by several members of the Nod-like receptor (NLR) family, although the precise mechanism for most of these remains elusive. NLRs consist of a family of about 20 proteins in mammals, which are capable of sensing microbial products as well as endogenous signals related to tissue injury. Here we provide an overview of our current understanding of the function of those NLRs in type I interferon responses with a focus on viral infections. We discuss how NLR-mediated type I interferon regulation can influence the development of auto-immunity and the immune response to infection. Citation: Kienes, I.; Weidl, T.; Mirza, Keywords: NOD-like receptors; Interferons; innate immunity; immune regulation; type I interferon; N.; Chamaillard, M.; Kufer, T.A. -
A Small De Novo 16Q24.1 Duplication in a Woman with Severe Clinical Features
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by HAL-Université de Bretagne Occidentale A small de novo 16q24.1 duplication in a woman with severe clinical features. Sylvia Qu´em´ener-Redon,Caroline B´enech, S´everine Audebert-Bellanger, Ga¨elleFriocourt, Marc Planes, Philippe Parent, Claude F´erec To cite this version: Sylvia Qu´em´ener-Redon, Caroline B´enech, S´everine Audebert-Bellanger, Ga¨elle Friocourt, Marc Planes, et al.. A small de novo 16q24.1 duplication in a woman with severe clini- cal features.. European Journal of Medical Genetics, Elsevier, 2013, epub ahead of print. <10.1016/j.ejmg.2013.01.001>. <inserm-00788405> HAL Id: inserm-00788405 http://www.hal.inserm.fr/inserm-00788405 Submitted on 14 Feb 2013 HAL is a multi-disciplinary open access L'archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destin´eeau d´ep^otet `ala diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publi´esou non, lished or not. The documents may come from ´emanant des ´etablissements d'enseignement et de teaching and research institutions in France or recherche fran¸caisou ´etrangers,des laboratoires abroad, or from public or private research centers. publics ou priv´es. A small de novo 16q24.1 duplication in a woman with severe clinical features Sylvia Quéméner-Redon1,2, Caroline Bénech1,3, Séverine Audebert-Bellanger4, Gaëlle Friocourt1, Marc Planes4, Philippe Parent4 and Claude Férec1,2,3 1 Institut National de la Santé et de la Recherche Médicale (INSERM), UMR1078, Brest, France, 2 Laboratoire de Génétique Moléculaire et d’Histocompatibilité, Centre Hospitalier Universitaire (CHU), Hôpital Morvan, Brest, France, 3 Etablissement Français du Sang (EFS) – Bretagne, Brest, France, 4Service de Pédiatrie et de Génétique Médicale, Centre Hospitalier Universitaire de Brest, Brest, France. -
Table 2. Significant
Table 2. Significant (Q < 0.05 and |d | > 0.5) transcripts from the meta-analysis Gene Chr Mb Gene Name Affy ProbeSet cDNA_IDs d HAP/LAP d HAP/LAP d d IS Average d Ztest P values Q-value Symbol ID (study #5) 1 2 STS B2m 2 122 beta-2 microglobulin 1452428_a_at AI848245 1.75334941 4 3.2 4 3.2316485 1.07398E-09 5.69E-08 Man2b1 8 84.4 mannosidase 2, alpha B1 1416340_a_at H4049B01 3.75722111 3.87309653 2.1 1.6 2.84852656 5.32443E-07 1.58E-05 1110032A03Rik 9 50.9 RIKEN cDNA 1110032A03 gene 1417211_a_at H4035E05 4 1.66015788 4 1.7 2.82772795 2.94266E-05 0.000527 NA 9 48.5 --- 1456111_at 3.43701477 1.85785922 4 2 2.8237185 9.97969E-08 3.48E-06 Scn4b 9 45.3 Sodium channel, type IV, beta 1434008_at AI844796 3.79536664 1.63774235 3.3 2.3 2.75319499 1.48057E-08 6.21E-07 polypeptide Gadd45gip1 8 84.1 RIKEN cDNA 2310040G17 gene 1417619_at 4 3.38875643 1.4 2 2.69163229 8.84279E-06 0.0001904 BC056474 15 12.1 Mus musculus cDNA clone 1424117_at H3030A06 3.95752801 2.42838452 1.9 2.2 2.62132809 1.3344E-08 5.66E-07 MGC:67360 IMAGE:6823629, complete cds NA 4 153 guanine nucleotide binding protein, 1454696_at -3.46081884 -4 -1.3 -1.6 -2.6026947 8.58458E-05 0.0012617 beta 1 Gnb1 4 153 guanine nucleotide binding protein, 1417432_a_at H3094D02 -3.13334396 -4 -1.6 -1.7 -2.5946297 1.04542E-05 0.0002202 beta 1 Gadd45gip1 8 84.1 RAD23a homolog (S. -
Single Nucleotide Polymorphisms Within Calcineurin-Encoding Genes
Annals of Applied Sport Science, vol. 4, no. 2, pp. 01-08, Summer 2016 DOI: 10.18869/acadpub.aassjournal.4.2.1 Original Article www.aassjournal.com www.AESAsport.com ISSN (Online): 2322 – 4479 Received: 06/03/2016 ISSN (Print): 2476–4981 Accepted: 26/06/2016 Single Nucleotide Polymorphisms within Calcineurin-Encoding Genes are Associated with Response to Aerobic Training in Han Chinese Males 1Rong-mei Xu, 2Tao Lu, 2Lingxian Yan, 1Qinghua Song* 1The Center of Physical Health, Henan Polytechnic University, Jiaozuo 454000, Henan Province, China. 2 The Lab of Human Body Science, Henan Polytechnic University, Jiaozuo 454000, Henan Province, China. ABSTRACT Calcineurin, which functions in calcium signaling, is expressed in skeletal and cardiac muscle and has been linked to sensitivity to muscle strength training. It is also proposed to contribute to individual aerobic endurance. To investigate the relationship between calcineurin-encoding genes and aerobic endurance traits, 126 young-adult Han Chinese males were enrolled in an aerobic exercise training study. Participants were genotyped for polymorphisms within the 5 genes (PPP3CA, PPP3CB, PPP3CC, PPP3R1 and PPP3R2) encoding calcineurin using restriction fragment length polymorphism polymerase chain reaction (PCR-RFLP) or matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Participants underwent 18 weeks of aerobic exercise training (running). Before and after the training period, maximal oxygen uptake (VO2max) and 12 km/h running economy were measured. Statistical analyses were performed using chi-square test and analysis of variance. The baseline value of VO2max was significantly associated with rs3804423 and rs2850965 loci in the PPP3CA gene (P<0.05). -
Role of NLRP3 Inflammasome Activation in Obesity-Mediated
International Journal of Environmental Research and Public Health Review Role of NLRP3 Inflammasome Activation in Obesity-Mediated Metabolic Disorders Kaiser Wani , Hind AlHarthi, Amani Alghamdi , Shaun Sabico and Nasser M. Al-Daghri * Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia; [email protected] (K.W.); [email protected] (H.A.); [email protected] (A.A.); [email protected] (S.S.) * Correspondence: [email protected]; Tel.: +966-14675939 Abstract: NLRP3 inflammasome is one of the multimeric protein complexes of the nucleotide-binding domain, leucine-rich repeat (NLR)-containing pyrin and HIN domain family (PYHIN). When ac- tivated, NLRP3 inflammasome triggers the release of pro-inflammatory interleukins (IL)-1β and IL-18, an essential step in innate immune response; however, defective checkpoints in inflamma- some activation may lead to autoimmune, autoinflammatory, and metabolic disorders. Among the consequences of NLRP3 inflammasome activation is systemic chronic low-grade inflammation, a cardinal feature of obesity and insulin resistance. Understanding the mechanisms involved in the regulation of NLRP3 inflammasome in adipose tissue may help in the development of specific inhibitors for the treatment and prevention of obesity-mediated metabolic diseases. In this narrative review, the current understanding of NLRP3 inflammasome activation and regulation is highlighted, including its putative roles in adipose tissue dysfunction and insulin resistance. Specific inhibitors of NLRP3 inflammasome activation which can potentially be used to treat metabolic disorders are also discussed. Keywords: NLRP3 inflammasome; metabolic stress; insulin resistance; diabetes; obesity Citation: Wani, K.; AlHarthi, H.; Alghamdi, A.; Sabico, S.; Al-Daghri, N.M. Role of NLRP3 Inflammasome 1. -
Supplementary Materials
1 Supplementary Materials: Supplemental Figure 1. Gene expression profiles of kidneys in the Fcgr2b-/- and Fcgr2b-/-. Stinggt/gt mice. (A) A heat map of microarray data show the genes that significantly changed up to 2 fold compared between Fcgr2b-/- and Fcgr2b-/-. Stinggt/gt mice (N=4 mice per group; p<0.05). Data show in log2 (sample/wild-type). 2 Supplemental Figure 2. Sting signaling is essential for immuno-phenotypes of the Fcgr2b-/-lupus mice. (A-C) Flow cytometry analysis of splenocytes isolated from wild-type, Fcgr2b-/- and Fcgr2b-/-. Stinggt/gt mice at the age of 6-7 months (N= 13-14 per group). Data shown in the percentage of (A) CD4+ ICOS+ cells, (B) B220+ I-Ab+ cells and (C) CD138+ cells. Data show as mean ± SEM (*p < 0.05, **p<0.01 and ***p<0.001). 3 Supplemental Figure 3. Phenotypes of Sting activated dendritic cells. (A) Representative of western blot analysis from immunoprecipitation with Sting of Fcgr2b-/- mice (N= 4). The band was shown in STING protein of activated BMDC with DMXAA at 0, 3 and 6 hr. and phosphorylation of STING at Ser357. (B) Mass spectra of phosphorylation of STING at Ser357 of activated BMDC from Fcgr2b-/- mice after stimulated with DMXAA for 3 hour and followed by immunoprecipitation with STING. (C) Sting-activated BMDC were co-cultured with LYN inhibitor PP2 and analyzed by flow cytometry, which showed the mean fluorescence intensity (MFI) of IAb expressing DC (N = 3 mice per group). 4 Supplemental Table 1. Lists of up and down of regulated proteins Accession No. -
36-2997: Anti-Calcineurin B / PPP3R1 Monoclonal Antibody(Clone: CALNB/2342)
9853 Pacific Heights Blvd. Suite D. San Diego, CA 92121, USA Tel: 858-263-4982 Email: [email protected] 36-2997: Anti-Calcineurin B / PPP3R1 Monoclonal Antibody(Clone: CALNB/2342) Clonality : Monoclonal Clone Name : CALNB/2342 Application : IHC Reactivity : Human Gene : PPP3R1 Gene ID : 5534 Uniprot ID : P63098 Calcineurin B, type I (19kDa); Calcineurin subunit B type 1; CALNB1; CNB1; PPP3R1 protein Alternative Name : phosphatase 3 (formerly 2B), regulatory subunit B, alpha isoform; Protein phosphatase 3 regulatory subunit B alpha; Protein phosphatase 3 regulatory subunit B alpha isoform 1 Isotype : Mouse IgG1, kappa Immunogen Information : Recombinant full-length Calcineurin B protein Description Calcineurin is an enzyme that dephosphorylates serine and threonine residues in proteins. It is a heterodimer of a 59kDa catalytic A subunit and a 19kDa regulatory B subunit that is activated by the binding of calcium ions and calmodulin. Calcineurin is expressed in many tissues, but its levels are highest in the brain, where it may play a role in learning and memory. It has many substrates, including NFAT, a transcription factor that is activated by dephosphorylation. Complexes of the immuno- suppressants cyclosporine and FK506 with immunophilin proteins such as cyclophilin and FKBP12 are potent and specific inhibitors of Calcineurin activity. Alterations in Calcineurin activity are suspected to play a role in cardiac hypertrophy and graft versus host disease in organ transplantation. Product Info Amount : 20 µg / 100 µg 200 µg/ml of Ab Purified from Bioreactor Concentrate by Protein A/G. Prepared in 10mM PBS with Content : 0.05% BSA & 0.05% azide. Also available WITHOUT BSA & azide at 1.0mg/ml. -
4-6 Weeks Old Female C57BL/6 Mice Obtained from Jackson Labs Were Used for Cell Isolation
Methods Mice: 4-6 weeks old female C57BL/6 mice obtained from Jackson labs were used for cell isolation. Female Foxp3-IRES-GFP reporter mice (1), backcrossed to B6/C57 background for 10 generations, were used for the isolation of naïve CD4 and naïve CD8 cells for the RNAseq experiments. The mice were housed in pathogen-free animal facility in the La Jolla Institute for Allergy and Immunology and were used according to protocols approved by the Institutional Animal Care and use Committee. Preparation of cells: Subsets of thymocytes were isolated by cell sorting as previously described (2), after cell surface staining using CD4 (GK1.5), CD8 (53-6.7), CD3ε (145- 2C11), CD24 (M1/69) (all from Biolegend). DP cells: CD4+CD8 int/hi; CD4 SP cells: CD4CD3 hi, CD24 int/lo; CD8 SP cells: CD8 int/hi CD4 CD3 hi, CD24 int/lo (Fig S2). Peripheral subsets were isolated after pooling spleen and lymph nodes. T cells were enriched by negative isolation using Dynabeads (Dynabeads untouched mouse T cells, 11413D, Invitrogen). After surface staining for CD4 (GK1.5), CD8 (53-6.7), CD62L (MEL-14), CD25 (PC61) and CD44 (IM7), naïve CD4+CD62L hiCD25-CD44lo and naïve CD8+CD62L hiCD25-CD44lo were obtained by sorting (BD FACS Aria). Additionally, for the RNAseq experiments, CD4 and CD8 naïve cells were isolated by sorting T cells from the Foxp3- IRES-GFP mice: CD4+CD62LhiCD25–CD44lo GFP(FOXP3)– and CD8+CD62LhiCD25– CD44lo GFP(FOXP3)– (antibodies were from Biolegend). In some cases, naïve CD4 cells were cultured in vitro under Th1 or Th2 polarizing conditions (3, 4). -
NOD-Like Receptors in the Eye: Uncovering Its Role in Diabetic Retinopathy
International Journal of Molecular Sciences Review NOD-like Receptors in the Eye: Uncovering Its Role in Diabetic Retinopathy Rayne R. Lim 1,2,3, Margaret E. Wieser 1, Rama R. Ganga 4, Veluchamy A. Barathi 5, Rajamani Lakshminarayanan 5 , Rajiv R. Mohan 1,2,3,6, Dean P. Hainsworth 6 and Shyam S. Chaurasia 1,2,3,* 1 Ocular Immunology and Angiogenesis Lab, University of Missouri, Columbia, MO 652011, USA; [email protected] (R.R.L.); [email protected] (M.E.W.); [email protected] (R.R.M.) 2 Department of Biomedical Sciences, University of Missouri, Columbia, MO 652011, USA 3 Ophthalmology, Harry S. Truman Memorial Veterans’ Hospital, Columbia, MO 652011, USA 4 Surgery, University of Missouri, Columbia, MO 652011, USA; [email protected] 5 Singapore Eye Research Institute, Singapore 169856, Singapore; [email protected] (V.A.B.); [email protected] (R.L.) 6 Mason Eye Institute, School of Medicine, University of Missouri, Columbia, MO 652011, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-573-882-3207 Received: 9 December 2019; Accepted: 27 January 2020; Published: 30 January 2020 Abstract: Diabetic retinopathy (DR) is an ocular complication of diabetes mellitus (DM). International Diabetic Federations (IDF) estimates up to 629 million people with DM by the year 2045 worldwide. Nearly 50% of DM patients will show evidence of diabetic-related eye problems. Therapeutic interventions for DR are limited and mostly involve surgical intervention at the late-stages of the disease. The lack of early-stage diagnostic tools and therapies, especially in DR, demands a better understanding of the biological processes involved in the etiology of disease progression. -
ATP-Binding and Hydrolysis in Inflammasome Activation
molecules Review ATP-Binding and Hydrolysis in Inflammasome Activation Christina F. Sandall, Bjoern K. Ziehr and Justin A. MacDonald * Department of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary, 3280 Hospital Drive NW, Calgary, AB T2N 4Z6, Canada; [email protected] (C.F.S.); [email protected] (B.K.Z.) * Correspondence: [email protected]; Tel.: +1-403-210-8433 Academic Editor: Massimo Bertinaria Received: 15 September 2020; Accepted: 3 October 2020; Published: 7 October 2020 Abstract: The prototypical model for NOD-like receptor (NLR) inflammasome assembly includes nucleotide-dependent activation of the NLR downstream of pathogen- or danger-associated molecular pattern (PAMP or DAMP) recognition, followed by nucleation of hetero-oligomeric platforms that lie upstream of inflammatory responses associated with innate immunity. As members of the STAND ATPases, the NLRs are generally thought to share a similar model of ATP-dependent activation and effect. However, recent observations have challenged this paradigm to reveal novel and complex biochemical processes to discern NLRs from other STAND proteins. In this review, we highlight past findings that identify the regulatory importance of conserved ATP-binding and hydrolysis motifs within the nucleotide-binding NACHT domain of NLRs and explore recent breakthroughs that generate connections between NLR protein structure and function. Indeed, newly deposited NLR structures for NLRC4 and NLRP3 have provided unique perspectives on the ATP-dependency of inflammasome activation. Novel molecular dynamic simulations of NLRP3 examined the active site of ADP- and ATP-bound models. The findings support distinctions in nucleotide-binding domain topology with occupancy of ATP or ADP that are in turn disseminated on to the global protein structure. -
Mutation in the COX4I1 Gene Is Associated with Short Stature, Poor Weight Gain and Increased Chromosomal Breaks, Simulating Fanconi Anemia
European Journal of Human Genetics (2017) 25, 1142–1146 & 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved 1018-4813/17 www.nature.com/ejhg ARTICLE Mutation in the COX4I1 gene is associated with short stature, poor weight gain and increased chromosomal breaks, simulating Fanconi anemia Bassam Abu-Libdeh*,1,4, Liza Douiev2,3,4, Sarah Amro1, Maher Shahrour1, Asaf Ta-Shma2, Chaya Miller2,3, Orly Elpeleg2 and Ann Saada*,2,3 We describe a novel autosomal recessive form of mitochondrial disease in a child with short stature, poor weight gain, and mild dysmorphic features with highly suspected Fanconi anemia due to a mutation in COX4I1 gene. Whole Exome Sequencing was performed then followed by Sanger confirmation, identified a K101N mutation in COX4I1, segregating with the disease. This nuclear gene encodes the common isoform of cytochrome c oxidase (COX) subunit 4 (COX 4-1), an integral regulatory part of COX (respiratory chain complex IV) the terminal electron acceptor of the mitochondrial respiratory chain. The patient’s fibroblasts disclosed decreased COX activity, impaired ATP production, elevated ROS production, decreased expression of COX4I1 mRNA and undetectable (COX4) protein. COX activity and ATP production were restored by lentiviral transfection with the wild-type gene. Our results demonstrate the first human mutation in the COX4I1 gene linked to diseases and confirm its role in the pathogenesis. Thus COX4I1 mutations should be considered in any patient with features suggestive of this diagnosis. European Journal of Human Genetics (2017) 25, 1142–1146; doi:10.1038/ejhg.2017.112; published online 2 August 2017 INTRODUCTION normal vaginal delivery with birth weight of 2.8 kg after an uneventful Mitochondrial cytochrome c oxidase (COX, complex IV) is the terminal pregnancy.