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  • 1
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    Continued clearance of apoptotic cells critically depends on the phagocyte Ucp2 protein (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-08-23
    Description: Rapid and efficient removal of apoptotic cells by phagocytes is important during development, tissue homeostasis and in immune responses. Efficient clearance depends on the capacity of a single phagocyte to ingest multiple apoptotic cells successively, and to process the corpse-derived cellular material. However, the factors that influence continued clearance by phagocytes are not known. Here we show that the mitochondrial membrane potential of the phagocyte critically controls engulfment capacity, with lower potential enhancing engulfment and vice versa. The mitochondrial membrane protein Ucp2, which acts to lower the mitochondrial membrane potential, was upregulated in phagocytes engulfing apoptotic cells. Loss of Ucp2 reduced phagocytic capacity, whereas Ucp2 overexpression enhanced engulfment. Mutational and pharmacological studies indicated a direct role for Ucp2-mediated mitochondrial function in phagocytosis. Macrophages from Ucp2-deficient mice were impaired in phagocytosis in vitro, and Ucp2-deficient mice showed profound in vivo defects in clearing dying cells in the thymus and testes. Collectively, these data indicate that mitochondrial membrane potential and Ucp2 are key molecular determinants of apoptotic cell clearance. As Ucp2 is linked to metabolic diseases and atherosclerosis, this newly discovered role for Ucp2 in apoptotic cell clearance has implications for the complex aetiology and pathogenesis of these diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3513690/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3513690/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Park, Daeho -- Han, Claudia Z -- Elliott, Michael R -- Kinchen, Jason M -- Trampont, Paul C -- Das, Soumita -- Collins, Sheila -- Lysiak, Jeffrey J -- Hoehn, Kyle L -- Ravichandran, Kodi S -- R01 GM064709/GM/NIGMS NIH HHS/ -- R01 HD057242/HD/NICHD NIH HHS/ -- T32 GM008136/GM/NIGMS NIH HHS/ -- England -- Nature. 2011 Aug 21;477(7363):220-4. doi: 10.1038/nature10340.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Cell Clearance, University of Virginia, Charlottesville, Virginia 22908, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21857682" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; Cell Line ; Cell Size/drug effects ; Cells, Cultured ; Ion Channels/deficiency/genetics/*metabolism ; Membrane Potential, Mitochondrial/drug effects/physiology ; Mice ; Mitochondrial Proteins/deficiency/genetics/*metabolism ; Phagocytes/*cytology/drug effects/*metabolism ; Phagocytosis/drug effects/*physiology ; Thymus Gland/cytology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Evolutionary implications of a third lymphocyte lineage in lampreys (2013)
    Nature Publishing Group (NPG)
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    Publication Date: 2013-08-13
    Description: Jawed vertebrates (gnathostomes) and jawless vertebrates (cyclostomes) have different adaptive immune systems. Gnathostomes use T- and B-cell antigen receptors belonging to the immunoglobulin superfamily. Cyclostomes, the lampreys and hagfish, instead use leucine-rich repeat proteins to construct variable lymphocyte receptors (VLRs), two types of which, VLRA and VLRB, are reciprocally expressed by lymphocytes resembling gnathostome T and B cells. Here we define another lineage of T-cell-like lymphocytes that express the recently identified VLRC receptors. Both VLRC(+) and VLRA(+) lymphocytes express orthologues of genes that gnathostome gammadelta and alphabeta T cells use for their differentiation, undergo VLRC and VLRA assembly and repertoire diversification in the 'thymoid' gill region, and express their VLRs solely as cell-surface proteins. Our findings suggest that the genetic programmes for two primordial T-cell lineages and a prototypic B-cell lineage were already present in the last common vertebrate ancestor approximately 500 million years ago. We propose that functional specialization of distinct T-cell-like lineages was an ancient feature of a primordial immune system.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901013/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901013/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hirano, Masayuki -- Guo, Peng -- McCurley, Nathanael -- Schorpp, Michael -- Das, Sabyasachi -- Boehm, Thomas -- Cooper, Max D -- R01 AI072435/AI/NIAID NIH HHS/ -- R01 GM100151/GM/NIGMS NIH HHS/ -- R01AI072435/AI/NIAID NIH HHS/ -- R01GM100151/GM/NIGMS NIH HHS/ -- England -- Nature. 2013 Sep 19;501(7467):435-8. doi: 10.1038/nature12467. Epub 2013 Aug 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Emory Vaccine Center and Department of Pathology and Laboratory Medicine, Emory University, 1462 Clifton Road North-East, Atlanta, Georgia 30322, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23934109" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens/immunology ; *Biological Evolution ; Cell Differentiation ; *Cell Lineage ; Gene Expression Profiling ; Lampreys/*immunology ; Mitogens/immunology ; Molecular Sequence Data ; Poly I-C/immunology ; Proteins/genetics/immunology/metabolism ; T-Lymphocyte Subsets/*cytology/*immunology/metabolism ; Transcription, Genetic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 3
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    NANOG-dependent function of TET1 and TET2 in establishment of pluripotency (2013)
    Nature Publishing Group (NPG)
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    Publication Date: 2013-02-12
    Description: Molecular control of the pluripotent state is thought to reside in a core circuitry of master transcription factors including the homeodomain-containing protein NANOG, which has an essential role in establishing ground state pluripotency during somatic cell reprogramming. Whereas the genomic occupancy of NANOG has been extensively investigated, comparatively little is known about NANOG-associated proteins and their contribution to the NANOG-mediated reprogramming process. Using enhanced purification techniques and a stringent computational algorithm, we identify 27 high-confidence protein interaction partners of NANOG in mouse embryonic stem cells. These consist of 19 previously unknown partners of NANOG that have not been reported before, including the ten-eleven translocation (TET) family methylcytosine hydroxylase TET1. We confirm physical association of NANOG with TET1, and demonstrate that TET1, in synergy with NANOG, enhances the efficiency of reprogramming. We also find physical association and reprogramming synergy of TET2 with NANOG, and demonstrate that knockdown of TET2 abolishes the reprogramming synergy of NANOG with a catalytically deficient mutant of TET1. These results indicate that the physical interaction between NANOG and TET1/TET2 proteins facilitates reprogramming in a manner that is dependent on the catalytic activity of TET1/TET2. TET1 and NANOG co-occupy genomic loci of genes associated with both maintenance of pluripotency and lineage commitment in embryonic stem cells, and TET1 binding is reduced upon NANOG depletion. Co-expression of NANOG and TET1 increases 5-hydroxymethylcytosine levels at the top-ranked common target loci Esrrb and Oct4 (also called Pou5f1), resulting in priming of their expression before reprogramming to naive pluripotency. We propose that TET1 is recruited by NANOG to enhance the expression of a subset of key reprogramming target genes. These results provide an insight into the reprogramming mechanism of NANOG and uncover a new role for 5-methylcytosine hydroxylases in the establishment of naive pluripotency.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3606645/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3606645/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Costa, Yael -- Ding, Junjun -- Theunissen, Thorold W -- Faiola, Francesco -- Hore, Timothy A -- Shliaha, Pavel V -- Fidalgo, Miguel -- Saunders, Arven -- Lawrence, Moyra -- Dietmann, Sabine -- Das, Satyabrata -- Levasseur, Dana N -- Li, Zhe -- Xu, Mingjiang -- Reik, Wolf -- Silva, Jose C R -- Wang, Jianlong -- 079249/Wellcome Trust/United Kingdom -- 086692/Wellcome Trust/United Kingdom -- 095645/Wellcome Trust/United Kingdom -- 1R01-GM095942-01A1/GM/NIGMS NIH HHS/ -- BB/H008071/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- G0700098/Medical Research Council/United Kingdom -- R01 GM095942/GM/NIGMS NIH HHS/ -- R01 HL112294/HL/NHLBI NIH HHS/ -- WT079249/Wellcome Trust/United Kingdom -- WT086692MA/Wellcome Trust/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- Medical Research Council/United Kingdom -- England -- Nature. 2013 Mar 21;495(7441):370-4. doi: 10.1038/nature11925. Epub 2013 Feb 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23395962" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cellular Reprogramming/*physiology ; DNA-Binding Proteins/genetics/*metabolism ; Embryonic Stem Cells ; Gene Expression Regulation, Developmental ; Genome ; Homeodomain Proteins/genetics/*metabolism ; Mice ; Protein Binding ; Proto-Oncogene Proteins/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 4
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    Pathogenomics of Culex quinquefasciatus and meta-analysis of infection responses to diverse pathogens (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-10-12
    Description: The mosquito Culex quinquefasciatus poses a substantial threat to human and veterinary health as a primary vector of West Nile virus (WNV), the filarial worm Wuchereria bancrofti, and an avian malaria parasite. Comparative phylogenomics revealed an expanded canonical C. quinquefasciatus immune gene repertoire compared with those of Aedes aegypti and Anopheles gambiae. Transcriptomic analysis of C. quinquefasciatus genes responsive to WNV, W. bancrofti, and non-native bacteria facilitated an unprecedented meta-analysis of 25 vector-pathogen interactions involving arboviruses, filarial worms, bacteria, and malaria parasites, revealing common and distinct responses to these pathogen types in three mosquito genera. Our findings provide support for the hypothesis that mosquito-borne pathogens have evolved to evade innate immune responses in three vector mosquito species of major medical importance.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3104938/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3104938/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bartholomay, Lyric C -- Waterhouse, Robert M -- Mayhew, George F -- Campbell, Corey L -- Michel, Kristin -- Zou, Zhen -- Ramirez, Jose L -- Das, Suchismita -- Alvarez, Kanwal -- Arensburger, Peter -- Bryant, Bart -- Chapman, Sinead B -- Dong, Yuemei -- Erickson, Sara M -- Karunaratne, S H P Parakrama -- Kokoza, Vladimir -- Kodira, Chinnappa D -- Pignatelli, Patricia -- Shin, Sang Woon -- Vanlandingham, Dana L -- Atkinson, Peter W -- Birren, Bruce -- Christophides, George K -- Clem, Rollie J -- Hemingway, Janet -- Higgs, Stephen -- Megy, Karine -- Ranson, Hilary -- Zdobnov, Evgeny M -- Raikhel, Alexander S -- Christensen, Bruce M -- Dimopoulos, George -- Muskavitch, Marc A T -- F31 AI080161/AI/NIAID NIH HHS/ -- F31 AI080161-01A1/AI/NIAID NIH HHS/ -- HHSN266200400001C/AO/NIAID NIH HHS/ -- HHSN266200400001C/PHS HHS/ -- HHSN266200400039C/AI/NIAID NIH HHS/ -- HHSN266200400039C/PHS HHS/ -- P20 RR017686/RR/NCRR NIH HHS/ -- P20 RR017686-01/RR/NCRR NIH HHS/ -- R01 AI019769/AI/NIAID NIH HHS/ -- R01 AI019769-26/AI/NIAID NIH HHS/ -- R01 AI059492/AI/NIAID NIH HHS/ -- R01 AI059492-05/AI/NIAID NIH HHS/ -- R01 AI061576/AI/NIAID NIH HHS/ -- R01 AI061576-08/AI/NIAID NIH HHS/ -- R01 AI067698/AI/NIAID NIH HHS/ -- R01 AI067698-05/AI/NIAID NIH HHS/ -- R01 AI078997/AI/NIAID NIH HHS/ -- R01 AI078997-02/AI/NIAID NIH HHS/ -- R01 AI095842/AI/NIAID NIH HHS/ -- R01 AI19769/AI/NIAID NIH HHS/ -- R01 AI59492/AI/NIAID NIH HHS/ -- R01 AI67698/AI/NIAID NIH HHS/ -- R21 AI067642/AI/NIAID NIH HHS/ -- R21 AI067642-01/AI/NIAID NIH HHS/ -- T01CCT622892/PHS HHS/ -- T32 A107536/PHS HHS/ -- T32 AI007414/AI/NIAID NIH HHS/ -- T32 AI007417/AI/NIAID NIH HHS/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2010 Oct 1;330(6000):88-90. doi: 10.1126/science.1193162.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Entomology, Iowa State University, Ames, IA 50011, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20929811" target="_blank"〉PubMed〈/a〉
    Keywords: Aedes/genetics/immunology/microbiology/parasitology ; Animals ; Anopheles gambiae/genetics/metabolism/microbiology/parasitology ; Arboviruses/immunology/pathogenicity/physiology ; Bacteria/immunology/pathogenicity ; Biological Evolution ; Culex/*genetics/*immunology/microbiology/parasitology ; Ecosystem ; Filarioidea/immunology/pathogenicity/physiology ; Gene Expression Profiling ; Gene Expression Regulation ; *Genes, Insect ; *Host-Pathogen Interactions ; Immunity, Innate/*genetics ; Insect Vectors/*genetics/*immunology/microbiology/parasitology ; Oligonucleotide Array Sequence Analysis ; Phylogeny ; RNA Interference ; Transcription, Genetic ; West Nile virus/immunology/pathogenicity/physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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