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  • 1
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    Requirement for type 2 NO synthase for IL-12 signaling in innate immunity (1999)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1999-05-13
    Description: Interleukin-12 (IL-12) and type 2 NO synthase (NOS2) are crucial for defense against bacterial and parasitic pathogens, but their relationship in innate immunity is unknown. In the absence of NOS2 activity, IL-12 was unable to prevent spreading of Leishmania parasites, did not stimulate natural killer (NK) cells for cytotoxicity or interferon-gamma (IFN-gamma) release, and failed to activate Tyk2 kinase and to tyrosine phosphorylate Stat4 (the central signal transducer of IL-12) in NK cells. Activation of Tyk2 in NK cells by IFN-alpha/beta also required NOS2. Thus, NOS2-derived NO is a prerequisite for cytokine signaling and function in innate immunity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Diefenbach, A -- Schindler, H -- Rollinghoff, M -- Yokoyama, W M -- Bogdan, C -- New York, N.Y. -- Science. 1999 May 7;284(5416):951-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut fur Klinische Mikrobiologie, Immunologie und Hygiene, Universitat Erlangen, Wasserturmstrasse 3, D-91054 Erlangen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10320373" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Cyclic GMP/metabolism ; Cytotoxicity, Immunologic ; DNA-Binding Proteins/metabolism ; Enzyme Activation ; Enzyme Inhibitors/pharmacology ; Immunity, Innate ; Interferon-gamma/biosynthesis/genetics ; Interferons/pharmacology ; Interleukin-12/pharmacology/*physiology ; Janus Kinase 2 ; Killer Cells, Natural/*immunology/metabolism ; *Leishmania major ; Leishmaniasis, Cutaneous/*immunology/metabolism ; Lysine/analogs & derivatives/pharmacology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Nitric Oxide/metabolism ; Nitric Oxide Synthase/antagonists & inhibitors/*metabolism ; Nitric Oxide Synthase Type II ; Phosphorylation ; Protein-Tyrosine Kinases/metabolism ; Proteins/metabolism ; *Proto-Oncogene Proteins ; STAT4 Transcription Factor ; *Signal Transduction ; TYK2 Kinase ; Trans-Activators/metabolism ; Up-Regulation
    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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  • 2
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    Regenerative biology: Innate immunity repairs gut lining (2015)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2015-12-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gronke, Konrad -- Diefenbach, Andreas -- England -- Nature. 2015 Dec 24;528(7583):488-9. doi: 10.1038/nature16325. Epub 2015 Dec 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Research Centre for Immunology, University of Mainz Medical Centre, and at the Institute of Medical Microbiology and Hygiene, 55131 Mainz, Germany. ; Max-Planck-Institute of Immunobiology and Epigenetics, Freiburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26649826" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Epithelial Cells/*cytology ; Female ; Humans ; Interleukins/*immunology ; Intestinal Mucosa/*cytology ; Intestine, Small/*cytology ; *Regeneration ; Stem Cells/*cytology/*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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  • 3
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    A T-bet gradient controls the fate and function of CCR6-RORgammat+ innate lymphoid cells (2013)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2013-01-22
    Description: At mucosal surfaces, the immune system should not initiate inflammatory immune responses to the plethora of antigens constantly present in the environment, but should remain poised to unleash a potent assault on intestinal pathogens. The transcriptional programs and regulatory factors required for immune cells to switch from homeostatic (often tissue-protective) function to potent antimicrobial immunity are poorly defined. Mucosal retinoic-acid-receptor-related orphan receptor-gammat-positive (RORgammat(+)) innate lymphoid cells (ILCs) are emerging as an important innate lymphocyte population required for immunity to intestinal infections. Various subsets of RORgammat(+) ILCs have been described but the transcriptional programs controlling their specification and fate remain largely unknown. Here we provide evidence that the transcription factor T-bet determines the fate of a distinct lineage of CCR6(-)RORgammat(+) ILCs. Postnatally emerging CCR6(-)RORgammat(+) ILCs upregulated T-bet and this was controlled by cues from the commensal microbiota and interleukin-23 (IL-23). In contrast, CCR6(+)RORgammat(+) ILCs, which arise earlier during ontogeny, did not express T-bet. T-bet instructed the expression of T-bet target genes such as interferon-gamma (IFN-gamma) and of the natural cytotoxicity receptor NKp46. Mice genetically lacking T-bet showed normal development of CCR6(-)RORgammat(+) ILCs, but they could not differentiate into NKp46-expressing RORgammat(+) ILCs (that is, IL-22-producing natural killer (NK-22) cells) and failed to produce IFN-gamma. The production of IFN-gamma by T-bet-expressing CCR6(-)RORgammat(+) ILCs was essential for the release of mucus-forming glycoproteins required to protect the epithelial barrier during Salmonella enterica infection. Salmonella infection also causes severe enterocolitis that is at least partly driven by IFN-gamma. Mice deficient for T-bet or depleted of ILCs developed only mild enterocolitis. Thus, graded expression of T-bet in CCR6(-)RORgammat(+) ILCs facilitates the differentiation of IFN-gamma-producing CCR6(-)RORgammat(+) ILCs required to protect the epithelial barrier against Salmonella infections. Co-expression of T-bet and RORgammat, which is also found in subsets of IL-17-producing T-helper (T(H)17) cells, may be an evolutionarily conserved transcriptional program that originally developed as part of the innate defence against infections but that also confers an increased risk of immune-mediated pathology.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Klose, Christoph S N -- Kiss, Elina A -- Schwierzeck, Vera -- Ebert, Karolina -- Hoyler, Thomas -- d'Hargues, Yannick -- Goppert, Nathalie -- Croxford, Andrew L -- Waisman, Ari -- Tanriver, Yakup -- Diefenbach, Andreas -- England -- Nature. 2013 Feb 14;494(7436):261-5. doi: 10.1038/nature11813. Epub 2013 Jan 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Medical Microbiology and Hygiene, University of Freiburg, Hermann-Herder-Strasse 11, D-79104 Freiburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23334414" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Ly/genetics ; Cell Differentiation ; *Cell Lineage ; Cells, Cultured ; Enterocolitis/immunology/metabolism/pathology ; Epithelium/immunology/metabolism/microbiology ; Immunity, Innate/*immunology ; Interferon-gamma/biosynthesis/genetics/immunology ; Interleukin-23/immunology ; Intestinal Mucosa/cytology/immunology/microbiology ; Lymphocytes/*cytology/*immunology/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mucus/secretion ; Natural Cytotoxicity Triggering Receptor 1/genetics ; Nuclear Receptor Subfamily 1, Group F, Member 3/*metabolism ; Receptors, CCR6/*deficiency/metabolism ; Salmonella Infections/immunology/metabolism ; Salmonella typhimurium/immunology/pathogenicity ; T-Box Domain Proteins/*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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    Natural aryl hydrocarbon receptor ligands control organogenesis of intestinal lymphoid follicles (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-10-29
    Description: Innate lymphoid cells (ILC) expressing the transcription factor RORgammat induce the postnatal formation of intestinal lymphoid follicles and regulate intestinal homeostasis. RORgammat(+) ILC express the aryl hydrocarbon receptor (AhR), a highly conserved, ligand-inducible transcription factor believed to control adaptation of multicellular organisms to environmental challenges. We show that AhR is required for the postnatal expansion of intestinal RORgammat(+) ILC and the formation of intestinal lymphoid follicles. AhR activity within RORgammat(+) ILC could be induced by dietary ligands such as those contained in vegetables of the family Brassicaceae. AhR-deficient mice were highly susceptible to infection with Citrobacter rodentium, a mouse model for attaching and effacing infections. Our results establish a molecular link between nutrients and the formation of immune system components required to maintain intestinal homeostasis and resistance to infections.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kiss, Elina A -- Vonarbourg, Cedric -- Kopfmann, Stefanie -- Hobeika, Elias -- Finke, Daniela -- Esser, Charlotte -- Diefenbach, Andreas -- New York, N.Y. -- Science. 2011 Dec 16;334(6062):1561-5. doi: 10.1126/science.1214914. Epub 2011 Oct 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Medical Microbiology and Hygiene, University of Freiburg Medical Center, Freiburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22033518" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Helix-Loop-Helix Transcription Factors/deficiency/genetics/*metabolism ; Cell Line, Tumor ; Citrobacter rodentium/immunology ; Diet ; Enterobacteriaceae Infections/immunology ; Intestine, Small/*cytology/immunology ; Ligands ; Lymphocytes/immunology/*metabolism ; Mice ; Mice, Inbred C57BL ; Organogenesis ; Receptors, Aryl Hydrocarbon/deficiency/genetics/*metabolism
    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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  • 5
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    Mass addition at Mount St. Helens, Washington, Inferred from Repeated Gravity Surveys (2018)
    Wiley
    Details
    Publication Date: 2018-01-22
    Description: Relative gravity measurements were made at 12 sites on Mount St. Helens and 4 sites far afield during the summers of 2010, 2012, 2014 and 2016. Positive residual gravity changes of 0.05–0.06±0.01 mGal from 2010-16 – a sign of mass addition – remain at proximal sites after accounting for the effects of changes in Crater Glacier shape and mass. Modeling of the 2010-16 monitoring data indicates mass addition in the volcano magma reservoir, the volcano conduit and/or the shallow hydrothermal aquifer. Magma intrusion in the volcano's known reservoir is suggested by the joint inversion of GPS and gravity data ( d = 5800±710 m b.s.l., Δ V m  = 49.8 ± 8.6 × 10 6 m 3 , ρ  = 1930 ± 300 kg/m 3 ); the modeled depth and location are consistent with that of the reservoir that fed the 2004–8 eruption, and its mass change can explain up to 19% of the residual gravity. The other two potential sources - the conduit and shallow aquifer - are not well constrained. Magma addition along the volcano conduit can explain up to 62% of the residual gravity ( Δ V m ≅ 31 × 10 6 m 3 , ρ m  ≅ 2300 kg/m 3 ). However, such an intrusion should have produced a measurable uplift, which is not observed in the GPS time series. Changes in the level of the volcano's shallow hydrothermal system ( ρ w  = 1000 kg/m 3 ) can explain 17% ( Δ V recharge ≅ 9 × 10 6 m 3 ) to 61% ( Δ V recharge ≅ 30 × 10 6 m 3 ) of the residual gravity. It would therefore seem that the bulk of the mass change measured at Mount St. Helens during 2010–16 was caused by shallow accumulation of water beneath the floor of the crater.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 6
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    Natural killer cell activation enhances immune pathology and promotes chronic infection by limiting CD8+ T-cell immunity (2011)
    National Academy of Sciences
    Details
    Publication Date: 2011-12-13
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 7
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    Natural killer cell activation enhances immune pathology and promotes chronic infection by limiting CD8+ T-cell immunity [Immunology] (2012)
    National Academy of Sciences
    Details
    Publication Date: 2012-01-25
    Description: Infections with HIV, hepatitis B virus, and hepatitis C virus can turn into chronic infections, which currently affect more than 500 million patients worldwide. It is generally thought that virus-mediated T-cell exhaustion limits T-cell function, thus promoting chronic disease. Here we demonstrate that natural killer (NK) cells have a negative impact on the development of T-cell immunity by using the murine lymphocytic choriomeningitis virus. NK cell-deficient (Nfil3−/−, E4BP4−/−) mice exhibited a higher virus-specific T-cell response. In addition, NK cell depletion caused enhanced T-cell immunity in WT mice, which led to rapid virus control and prevented chronic infection in lymphocytic choriomeningitis virus clone 13- and reduced viral load in DOCILE-infected animals. Further experiments showed that NKG2D triggered regulatory NK cell functions, which were mediated by perforin, and limited T-cell responses. Therefore, we identified an important role of regulatory NK cells in limiting T-cell immunity during virus infection.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 8
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    Geomorphic expression of rapid Holocene silicic magma reservoir growth beneath Laguna del Maule, Chile (2018)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2018-06-28
    Description: Large rhyolitic volcanoes pose a hazard, yet the processes and signals foretelling an eruption are obscure. Satellite geodesy has revealed surface inflation signaling unrest within magma reservoirs underlying a few rhyolitic volcanoes. Although seismic, electrical, and potential field methods may illuminate the current configuration and state of these reservoirs, they cannot fully address the processes by which they grow and evolve on geologic time scales. We combine measurement of a deformed paleoshore surface, isotopic dating of volcanism and surface exposure, and modeling to determine the rate of growth of a rhyolite-producing magma reservoir. The numerical approach builds on a magma intrusion model developed to explain the current, decade-long, surface inflation at 〉20 cm/year. Assuming that the observed 62-m uplift reflects several non-eruptive intrusions of magma, each similar to the unrest over the past decade, we find that ~13 km 3 of magma recharged the reservoir at a depth of ~7 km during the Holocene, accompanied by the eruption of ~9 km 3 of rhyolite. The long-term rate of magma input is consistent with reservoir freezing and pluton formation. Yet, the unique set of observations considered here implies that large reservoirs can be incubated and grow at shallow depth via episodic high-flux magma injections. These replenishment episodes likely drive rapid inflation, destabilize cooling systems, propel rhyolitic eruptions, and thus should be carefully monitored.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 9
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    Cyclic lava effusion during the 2018 eruption of Kilauea Volcano (2019)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2019
    Description: 〈p〉Lava flows present a recurring threat to communities on active volcanoes, and volumetric eruption rate is one of the primary factors controlling flow behavior and hazard. The time scales and driving forces of eruption rate variability, however, remain poorly understood. In 2018, a highly destructive eruption occurred on the lower flank of Kīlauea Volcano, Hawai‘i, where the primary vent exhibited substantial cyclic eruption rates on both short (minutes) and long (tens of hours) time scales. We used multiparameter data to show that the short cycles were driven by shallow outgassing, whereas longer cycles were pressure-driven surges in magma supply triggered by summit caldera collapse events 40 kilometers upslope. The results provide a clear link between eruption rate fluctuations and their driving processes in the magmatic system.〈/p〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
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    Mass Addition at Mount St. Helens, Washington, Inferred From Repeated Gravity Surveys (2018)
    American Geophysical Union
    Details
    Publication Date: 2018-02-01
    Description: Relative gravity measurements were made at 12 sites on Mount St. Helens and 4 sites far afield during the summers of 2010, 2012, 2014, and 2016. Positive residual gravity changes of 0.05–0.06 ± 0.01 mGal from 2010 to 2016—a sign of mass addition—remain at proximal sites after accounting for the effects of changes in Crater Glacier shape and mass. Modeling of the 2010–2016 monitoring data indicates mass addition in the volcano magma reservoir, the volcano conduit, and/or the shallow hydrothermal aquifer. Magma intrusion in the volcano's known reservoir is suggested by the joint inversion of GPS and gravity data (d = 5800 ± 710 m below sea level, ΔVm = 49.8 ± 8.6 × 106m3, ρ = 1930 ± 300 kg/m3); the modeled depth and location are consistent with that of the reservoir that fed the 2004–2008 eruption, and its mass change can explain up to 19% of the residual gravity. The other two potential sources—the conduit and shallow aquifer—are not well constrained. Magma addition along the volcano conduit can explain up to 62% of the residual gravity (ΔVm ≅ 31 × 106m3, ρm ≅ 2, 300 kg/m3). However, such an intrusion should have produced a measurable surface deformation, which is not observed in the GPS time series. Changes in the level of the volcano's shallow hydrothermal system (ρw = 1, 000 kg/m3) can explain 17% (ΔVrecharge ≅ 9 × 106m3) to 61% (ΔVrecharge ≅ 30 × 106m3) of the residual gravity. It would therefore seem that the bulk of the mass change measured at Mount St. Helens during 2010–2016 was caused by shallow accumulation of water beneath the floor of the crater. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.
    Print ISSN: 2169-9313
    Electronic ISSN: 2169-9356
    Topics: Geosciences , Physics
    Published by American Geophysical Union
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