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Ronald N Germain

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https://www.readbyqxmd.com/read/28190711/cd8-t-cells-orchestrate-pdc-xcr1-dendritic-cell-spatial-and-functional-cooperativity-to-optimize-priming
#1
Anna Brewitz, Sarah Eickhoff, Sabrina Dähling, Thomas Quast, Sammy Bedoui, Richard A Kroczek, Christian Kurts, Natalio Garbi, Winfried Barchet, Matteo Iannacone, Frederick Klauschen, Waldemar Kolanus, Tsuneyasu Kaisho, Marco Colonna, Ronald N Germain, Wolfgang Kastenmüller
Adaptive cellular immunity is initiated by antigen-specific interactions between T lymphocytes and dendritic cells (DCs). Plasmacytoid DCs (pDCs) support antiviral immunity by linking innate and adaptive immune responses. Here we examined pDC spatiotemporal dynamics during viral infection to uncover when, where, and how they exert their functions. We found that pDCs accumulated at sites of CD8(+) T cell antigen-driven activation in a CCR5-dependent fashion. Furthermore, activated CD8(+) T cells orchestrated the local recruitment of lymph node-resident XCR1 chemokine receptor-expressing DCs via secretion of the XCL1 chemokine...
February 8, 2017: Immunity
https://www.readbyqxmd.com/read/28130403/suppression-of-lethal-autoimmunity-by-regulatory-t-cells-with-a-single-tcr-specificity
#2
Andrew G Levine, Saskia Hemmers, Antonio P Baptista, Michail Schizas, Mehlika B Faire, Bruno Moltedo, Catherine Konopacki, Marc Schmidt-Supprian, Ronald N Germain, Piper M Treuting, Alexander Y Rudensky
The regulatory T cell (T reg cell) T cell receptor (TCR) repertoire is highly diverse and skewed toward recognition of self-antigens. TCR expression by T reg cells is continuously required for maintenance of immune tolerance and for a major part of their characteristic gene expression signature; however, it remains unknown to what degree diverse TCR-mediated interactions with cognate self-antigens are required for these processes. In this study, by experimentally switching the T reg cell TCR repertoire to a single T reg cell TCR, we demonstrate that T reg cell function and gene expression can be partially uncoupled from TCR diversity...
January 27, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28100833/follicular-cd8-t-cells-accumulate-in-hiv-infection-and-can-kill-infected-cells-in-vitro-via-bispecific-antibodies
#3
Constantinos Petrovas, Sara Ferrando-Martinez, Michael Y Gerner, Joseph P Casazza, Amarendra Pegu, Claire Deleage, Arik Cooper, Jason Hataye, Sarah Andrews, David Ambrozak, Perla M Del Río Estrada, Eli Boritz, Robert Paris, Eirini Moysi, Kristin L Boswell, Ezequiel Ruiz-Mateos, Ilias Vagios, Manuel Leal, Yuria Ablanedo-Terrazas, Amaranta Rivero, Luz Alicia Gonzalez-Hernandez, Adrian B McDermott, Susan Moir, Gustavo Reyes-Terán, Fernando Docobo, Giuseppe Pantaleo, Daniel C Douek, Michael R Betts, Jacob D Estes, Ronald N Germain, John R Mascola, Richard A Koup
Cytolytic CD8 T cells play a crucial role in the control and elimination of virus-infected cells and are a major focus of HIV cure efforts. However, it has been shown that HIV-specific CD8 T cells are infrequently found within germinal centers (GCs), a predominant site of active and latent HIV infection. We demonstrate that HIV infection induces marked changes in the phenotype, frequency, and localization of CD8 T cells within the lymph node (LN). Significantly increased frequencies of CD8 T cells in the B cell follicles and GCs were found in LNs from treated and untreated HIV-infected individuals...
January 18, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28091576/adjuvant-and-carrier-protein-dependent-t-cell-priming-promotes-a-robust-antibody-response-against-the-plasmodium-falciparum-pfs25-vaccine-candidate
#4
Andrea J Radtke, Charles F Anderson, Nicolas Riteau, Kelly Rausch, Puthupparampil Scaria, Emily R Kelnhofer, Randall F Howard, Alan Sher, Ronald N Germain, Patrick Duffy
Humoral immune responses have the potential to maintain protective antibody levels for years due to the immunoglobulin-secreting activity of long-lived plasma cells (LLPCs). However, many subunit vaccines under development fail to generate robust LLPC responses, and therefore a variety of strategies are being employed to overcome this limitation, including conjugation to carrier proteins and/or formulation with potent adjuvants. Pfs25, an antigen expressed on malaria zygotes and ookinetes, is a leading transmission blocking vaccine (TBV) candidate for Plasmodium falciparum...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/27903737/allergen-induced-cd4-t-cell-cytokine-production-within-airway-mucosal-dendritic-cell-t-cell-clusters-drives-the-local-recruitment-of-myeloid-effector-cells
#5
Tibor Z Veres, Tamás Kopcsányi, Nicholas van Panhuys, Michael Y Gerner, Zhiduo Liu, Pia Rantakari, Johannes Dunkel, Masayuki Miyasaka, Marko Salmi, Sirpa Jalkanen, Ronald N Germain
Allergic asthma develops in the mucosal tissue of small bronchi. At these sites, local cytokine production by Th2/Th17 cells is believed to be critical for the development of tissue eosinophilia/neutrophilia. Using the mouse trachea as a relevant model of human small airways, we performed advanced in vivo dynamic and in situ static imaging to visualize individual cytokine-producing T cells in the airway mucosa and to define their immediate cellular environment. Upon allergen sensitization, newly recruited CD4(+) T cells formed discrete Ag-driven clusters with dendritic cells (DCs)...
January 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27618452/the-genetics-of-blood-pressure-regulation-and-its-target-organs-from-association-studies-in-342-415-individuals
#6
Georg B Ehret, Teresa Ferreira, Daniel I Chasman, Anne U Jackson, Ellen M Schmidt, Toby Johnson, Gudmar Thorleifsson, Jian'an Luan, Louise A Donnelly, Stavroula Kanoni, Ann-Kristin Petersen, Vasyl Pihur, Rona J Strawbridge, Dmitry Shungin, Maria F Hughes, Osorio Meirelles, Marika Kaakinen, Nabila Bouatia-Naji, Kati Kristiansson, Sonia Shah, Marcus E Kleber, Xiuqing Guo, Leo-Pekka Lyytikäinen, Cristiano Fava, Niclas Eriksson, Ilja M Nolte, Patrik K Magnusson, Elias L Salfati, Loukianos S Rallidis, Elizabeth Theusch, Andrew J P Smith, Lasse Folkersen, Kate Witkowska, Tune H Pers, Roby Joehanes, Stuart K Kim, Lazaros Lataniotis, Rick Jansen, Andrew D Johnson, Helen Warren, Young Jin Kim, Wei Zhao, Ying Wu, Bamidele O Tayo, Murielle Bochud, Devin Absher, Linda S Adair, Najaf Amin, Dan E Arking, Tomas Axelsson, Damiano Baldassarre, Beverley Balkau, Stefania Bandinelli, Michael R Barnes, Inês Barroso, Stephen Bevan, Joshua C Bis, Gyda Bjornsdottir, Michael Boehnke, Eric Boerwinkle, Lori L Bonnycastle, Dorret I Boomsma, Stefan R Bornstein, Morris J Brown, Michel Burnier, Claudia P Cabrera, John C Chambers, I-Shou Chang, Ching-Yu Cheng, Peter S Chines, Ren-Hua Chung, Francis S Collins, John M Connell, Angela Döring, Jean Dallongeville, John Danesh, Ulf de Faire, Graciela Delgado, Anna F Dominiczak, Alex S F Doney, Fotios Drenos, Sarah Edkins, John D Eicher, Roberto Elosua, Stefan Enroth, Jeanette Erdmann, Per Eriksson, Tonu Esko, Evangelos Evangelou, Alun Evans, Tove Fall, Martin Farrall, Janine F Felix, Jean Ferrières, Luigi Ferrucci, Myriam Fornage, Terrence Forrester, Nora Franceschini, Oscar H Franco, Anders Franco-Cereceda, Ross M Fraser, Santhi K Ganesh, He Gao, Karl Gertow, Francesco Gianfagna, Bruna Gigante, Franco Giulianini, Anuj Goel, Alison H Goodall, Mark O Goodarzi, Mathias Gorski, Jürgen Gräßler, Christopher J Groves, Vilmundur Gudnason, Ulf Gyllensten, Göran Hallmans, Anna-Liisa Hartikainen, Maija Hassinen, Aki S Havulinna, Caroline Hayward, Serge Hercberg, Karl-Heinz Herzig, Andrew A Hicks, Aroon D Hingorani, Joel N Hirschhorn, Albert Hofman, Jostein Holmen, Oddgeir Lingaas Holmen, Jouke-Jan Hottenga, Phil Howard, Chao A Hsiung, Steven C Hunt, M Arfan Ikram, Thomas Illig, Carlos Iribarren, Richard A Jensen, Mika Kähönen, Hyun Min Kang, Sekar Kathiresan, Brendan J Keating, Kay-Tee Khaw, Yun Kyoung Kim, Eric Kim, Mika Kivimaki, Norman Klopp, Genovefa Kolovou, Pirjo Komulainen, Jaspal S Kooner, Gulum Kosova, Ronald M Krauss, Diana Kuh, Zoltan Kutalik, Johanna Kuusisto, Kirsti Kvaløy, Timo A Lakka, Nanette R Lee, I-Te Lee, Wen-Jane Lee, Daniel Levy, Xiaohui Li, Kae-Woei Liang, Honghuang Lin, Li Lin, Jaana Lindström, Stéphane Lobbens, Satu Männistö, Gabriele Müller, Martina Müller-Nurasyid, François Mach, Hugh S Markus, Eirini Marouli, Mark I McCarthy, Colin A McKenzie, Pierre Meneton, Cristina Menni, Andres Metspalu, Vladan Mijatovic, Leena Moilanen, May E Montasser, Andrew D Morris, Alanna C Morrison, Antonella Mulas, Ramaiah Nagaraja, Narisu Narisu, Kjell Nikus, Christopher J O'Donnell, Paul F O'Reilly, Ken K Ong, Fred Paccaud, Cameron D Palmer, Afshin Parsa, Nancy L Pedersen, Brenda W Penninx, Markus Perola, Annette Peters, Neil Poulter, Peter P Pramstaller, Bruce M Psaty, Thomas Quertermous, Dabeeru C Rao, Asif Rasheed, N William Rayner, Frida Renström, Rainer Rettig, Kenneth M Rice, Robert Roberts, Lynda M Rose, Jacques Rossouw, Nilesh J Samani, Serena Sanna, Jouko Saramies, Heribert Schunkert, Sylvain Sebert, Wayne H-H Sheu, Young-Ah Shin, Xueling Sim, Johannes H Smit, Albert V Smith, Maria X Sosa, Tim D Spector, Alena Stančáková, Alice V Stanton, Kathleen E Stirrups, Heather M Stringham, Johan Sundstrom, Amy J Swift, Ann-Christine Syvänen, E-Shyong Tai, Toshiko Tanaka, Kirill V Tarasov, Alexander Teumer, Unnur Thorsteinsdottir, Martin D Tobin, Elena Tremoli, Andre G Uitterlinden, Matti Uusitupa, Ahmad Vaez, Dhananjay Vaidya, Cornelia M van Duijn, Erik P A van Iperen, Ramachandran S Vasan, Germaine C Verwoert, Jarmo Virtamo, Veronique Vitart, Benjamin F Voight, Peter Vollenweider, Aline Wagner, Louise V Wain, Nicholas J Wareham, Hugh Watkins, Alan B Weder, Harm-Jan Westra, Rainford Wilks, Tom Wilsgaard, James F Wilson, Tien Y Wong, Tsun-Po Yang, Jie Yao, Loic Yengo, Weihua Zhang, Jing Hua Zhao, Xiaofeng Zhu, Pascal Bovet, Richard S Cooper, Karen L Mohlke, Danish Saleheen, Jong-Young Lee, Paul Elliott, Hinco J Gierman, Cristen J Willer, Lude Franke, G Kees Hovingh, Kent D Taylor, George Dedoussis, Peter Sever, Andrew Wong, Lars Lind, Themistocles L Assimes, Inger Njølstad, Peter E H Schwarz, Claudia Langenberg, Harold Snieder, Mark J Caulfield, Olle Melander, Markku Laakso, Juha Saltevo, Rainer Rauramaa, Jaakko Tuomilehto, Erik Ingelsson, Terho Lehtimäki, Kristian Hveem, Walter Palmas, Winfried März, Meena Kumari, Veikko Salomaa, Yii-Der I Chen, Jerome I Rotter, Philippe Froguel, Marjo-Riitta Jarvelin, Edward G Lakatta, Kari Kuulasmaa, Paul W Franks, Anders Hamsten, H-Erich Wichmann, Colin N A Palmer, Kari Stefansson, Paul M Ridker, Ruth J F Loos, Aravinda Chakravarti, Panos Deloukas, Andrew P Morris, Christopher Newton-Cheh, Patricia B Munroe
To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues...
October 2016: Nature Genetics
https://www.readbyqxmd.com/read/27501248/defining-cd8-t-cells-that-provide-the-proliferative-burst-after-pd-1-therapy
#7
Se Jin Im, Masao Hashimoto, Michael Y Gerner, Junghwa Lee, Haydn T Kissick, Matheus C Burger, Qiang Shan, J Scott Hale, Judong Lee, Tahseen H Nasti, Arlene H Sharpe, Gordon J Freeman, Ronald N Germain, Helder I Nakaya, Hai-Hui Xue, Rafi Ahmed
Chronic viral infections are characterized by a state of CD8(+) T-cell dysfunction that is associated with expression of the programmed cell death 1 (PD-1) inhibitory receptor. A better understanding of the mechanisms that regulate CD8(+) T-cell responses during chronic infection is required to improve immunotherapies that restore function in exhausted CD8(+) T cells. Here we identify a population of virus-specific CD8(+) T cells that proliferate after blockade of the PD-1 inhibitory pathway in mice chronically infected with lymphocytic choriomeningitis virus (LCMV)...
September 15, 2016: Nature
https://www.readbyqxmd.com/read/27237739/distinct-nf-%C3%AE%C2%BAb-and-mapk-activation-thresholds-uncouple-steady-state-microbe-sensing-from-anti-pathogen-inflammatory-responses
#8
Rachel A Gottschalk, Andrew J Martins, Bastian R Angermann, Bhaskar Dutta, Caleb E Ng, Stefan Uderhardt, John S Tsang, Iain D C Fraser, Martin Meier-Schellersheim, Ronald N Germain
The innate immune system distinguishes low-level homeostatic microbial stimuli from those of invasive pathogens, yet we lack understanding of how qualitatively similar microbial products yield context-specific macrophage functional responses. Using quantitative approaches, we found that NF-κB and MAPK signaling was activated at different concentrations of a stimulatory TLR4 ligand in both mouse and human macrophages. Above a threshold of ligand, MAPK were activated in a switch-like manner, facilitating production of inflammatory mediators...
June 22, 2016: Cell Systems
https://www.readbyqxmd.com/read/27064162/william-e-paul-md-1936-2015
#9
Ronald N Germain, B J Fowlkes, Lawrence E Samelson, Warren J Leonard
No abstract text is available yet for this article.
December 2015: Trends in Immunology
https://www.readbyqxmd.com/read/26997126/corrigendum-an-interactive-web-based-application-for-comprehensive-analysis-of-rnai-screen-data
#10
Bhaskar Dutta, Alaleh Azhir, Louis-Henri Merino, Yongjian Guo, Swetha Revanur, Piyush B Madhamshettiwar, Ronald N Germain, Jennifer A Smith, Kaylene J Simpson, Scott E Martin, Eugen Buehler, Iain D C Fraser
No abstract text is available yet for this article.
March 21, 2016: Nature Communications
https://www.readbyqxmd.com/read/26902267/an-interactive-web-based-application-for-comprehensive-analysis-of-rnai-screen-data
#11
Bhaskar Dutta, Alaleh Azhir, Louis-Henri Merino, Yongjian Guo, Swetha Revanur, Piyush B Madhamshettiwar, Ronald N Germain, Jennifer A Smith, Kaylene J Simpson, Scott E Martin, Eugen Buehler, Eugen Beuhler, Iain D C Fraser
RNAi screens are widely used in functional genomics. Although the screen data can be susceptible to a number of experimental biases, many of these can be corrected by computational analysis. For this purpose, here we have developed a web-based platform for integrated analysis and visualization of RNAi screen data named CARD (for Comprehensive Analysis of RNAi Data; available at https://card.niaid.nih.gov). CARD allows the user to seamlessly carry out sequential steps in a rigorous data analysis workflow, including normalization, off-target analysis, integration of gene expression data, optimal thresholds for hit selection and network/pathway analysis...
February 23, 2016: Nature Communications
https://www.readbyqxmd.com/read/26788561/william-e-paul-m-d-1936%C3%A2-2015
#12
Ronald N Germain, B J Fowlkes, Lawrence E Samelson, Warren J Leonard
No abstract text is available yet for this article.
October 20, 2015: Immunity
https://www.readbyqxmd.com/read/26637660/william-e-paul-m-d-1936-2015-president-the-american-association-of-immunologists-1986-1987
#13
Ronald N Germain
No abstract text is available yet for this article.
December 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/26605524/immune-homeostasis-enforced-by-co-localized-effector-and-regulatory-t-cells
#14
Zhiduo Liu, Michael Y Gerner, Nicholas Van Panhuys, Andrew G Levine, Alexander Y Rudensky, Ronald N Germain
FOXP3(+) regulatory T cells (Treg cells) prevent autoimmunity by limiting the effector activity of T cells that have escaped thymic negative selection or peripheral inactivation. Despite the information available about molecular factors mediating the suppressive function of Treg cells, the relevant cellular events in intact tissues remain largely unexplored, and whether Treg cells prevent activation of self-specific T cells or primarily limit damage from such cells has not been determined. Here we use multiplex, quantitative imaging in mice to show that, within secondary lymphoid tissues, highly suppressive Treg cells expressing phosphorylated STAT5 exist in discrete clusters with rare IL-2-positive T cells that are activated by self-antigens...
December 10, 2015: Nature
https://www.readbyqxmd.com/read/26469035/william-e-paul-1936-2015
#15
Ronald N Germain
No abstract text is available yet for this article.
October 15, 2015: Nature
https://www.readbyqxmd.com/read/26451485/microbiota-dependent-sequelae-of-acute-infection-compromise-tissue-specific-immunity
#16
Denise Morais da Fonseca, Timothy W Hand, Seong-Ji Han, Michael Y Gerner, Arielle Glatman Zaretsky, Allyson L Byrd, Oliver J Harrison, Alexandra M Ortiz, Mariam Quinones, Giorgio Trinchieri, Jason M Brenchley, Igor E Brodsky, Ronald N Germain, Gwendalyn J Randolph, Yasmine Belkaid
Infections have been proposed as initiating factors for inflammatory disorders; however, identifying associations between defined infectious agents and the initiation of chronic disease has remained elusive. Here, we report that a single acute infection can have dramatic and long-term consequences for tissue-specific immunity. Following clearance of Yersinia pseudotuberculosis, sustained inflammation and associated lymphatic leakage in the mesenteric adipose tissue deviates migratory dendritic cells to the adipose compartment, thereby preventing their accumulation in the mesenteric lymph node...
October 8, 2015: Cell
https://www.readbyqxmd.com/read/26347474/nk-dc-crosstalk-controls-the-autopathogenic-th17-response-through-an-innate-ifn-%C3%AE-il-27-axis
#17
Wai Po Chong, Nicholas van Panhuys, Jun Chen, Phyllis B Silver, Yingyos Jittayasothorn, Mary J Mattapallil, Ronald N Germain, Rachel R Caspi
IFN-γ is a pathogenic cytokine involved in inflammation. Paradoxically, its deficiency exacerbates experimental autoimmune encephalomyelitis, uveitis, and arthritis. Here, we demonstrate using IFN-γ(-/-) mice repleted with IFN-γ +/+: NK cells that innate production of IFN-γ from NK cells is necessary and sufficient to trigger an endogenous regulatory circuit that limits autoimmunity. After immunization, DCs recruited IFN-γ-producing NK cells to the draining lymph node and interacted with them in a CXCR3-dependent fashion...
September 21, 2015: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/26199343/targeted-proteomics-driven-computational-modeling-of-macrophage-s1p-chemosensing
#18
Nathan P Manes, Bastian R Angermann, Marijke Koppenol-Raab, Eunkyung An, Virginie H Sjoelund, Jing Sun, Masaru Ishii, Ronald N Germain, Martin Meier-Schellersheim, Aleksandra Nita-Lazar
Osteoclasts are monocyte-derived multinuclear cells that directly attach to and resorb bone. Sphingosine-1-phosphate (S1P)(1) regulates bone resorption by functioning as both a chemoattractant and chemorepellent of osteoclast precursors through two G-protein coupled receptors that antagonize each other in an S1P-concentration-dependent manner. To quantitatively explore the behavior of this chemosensing pathway, we applied targeted proteomics, transcriptomics, and rule-based pathway modeling using the Simmune toolset...
October 2015: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/26167641/continuous-volumetric-imaging-via-an-optical-phase-locked-ultrasound-lens
#19
Lingjie Kong, Jianyong Tang, Justin P Little, Yang Yu, Tim Lämmermann, Charles P Lin, Ronald N Germain, Meng Cui
In vivo imaging at high spatiotemporal resolution is key to the understanding of complex biological systems. We integrated an optical phase-locked ultrasound lens into a two-photon fluorescence microscope and achieved microsecond-scale axial scanning, thus enabling volumetric imaging at tens of hertz. We applied this system to multicolor volumetric imaging of processes sensitive to motion artifacts, including calcium dynamics in behaving mouse brain and transient morphology changes and trafficking of immune cells...
August 2015: Nature Methods
https://www.readbyqxmd.com/read/26091028/healing-the-nih-funded-biomedical-research-enterprise
#20
Ronald N Germain
Many feel that the R01 grant system supporting biomedical research in the U.S. is broken, discouraging entry of young investigators into the system and inadequately supporting more established investigators. Here, I argue for a "person-not-project"-based scheme that would permit creative, unfettered research by new investigators, better tie ongoing research contributions to continued funding, and help match the number of investigators seeking support with available funds.
June 18, 2015: Cell
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