TY - JOUR A1 - Welz, M. A1 - Eickhoff, S. A1 - Abdullah, Z. A1 - Trebicka, J. A1 - Gartlan, K. H. A1 - Spicer, J. A. A1 - Demetris, A. J. A1 - Akhlaghi, H. A1 - Anton, M. A1 - Manske, K. A1 - Zehn, D. A1 - Nieswandt, B. A1 - Kurts, C. A1 - Trapani, J. A. A1 - Knolle, P. A1 - Wohlleber, D. A1 - Kastenmüller, W. T1 - Perforin inhibition protects from lethal endothelial damage during fulminant viral hepatitis JF - Nature Communications N2 - CD8 T cells protect the liver against viral infection, but can also cause severe liver damage that may even lead to organ failure. Given the lack of mechanistic insights and specific treatment options in patients with acute fulminant hepatitis, we develop a mouse model reflecting a severe acute virus-induced CD8 T cell-mediated hepatitis. Here we show that antigen-specific CD8 T cells induce liver damage in a perforin-dependent manner, yet liver failure is not caused by effector responses targeting virus-infected hepatocytes alone. Additionally, CD8 T cell mediated elimination of cross-presenting liver sinusoidal endothelial cells causes endothelial damage that leads to a dramatically impaired sinusoidal perfusion and indirectly to hepatocyte death. With the identification of perforin-mediated killing as a critical pathophysiologic mechanism of liver failure and the protective function of a new class of perforin inhibitor, our study opens new potential therapeutic angles for fulminant viral hepatitis. KW - cytotoxic T cells KW - hepatology KW - imaging the immune system KW - viral infection Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-233593 VL - 9 ER - TY - JOUR A1 - Levitis, Elizabeth A1 - Gould van Praag, Cassandra D A1 - Gau, Rémi A1 - Heunis, Stephan A1 - DuPre, Elizabeth A1 - Kiar, Gregory A1 - Bottenhorn, Katherine L A1 - Glatard, Tristan A1 - Nikolaidis, Aki A1 - Whitaker, Kirstie Jane A1 - Mancini, Matteo A1 - Niso, Guiomar A1 - Afyouni, Soroosh A1 - Alonso-Ortiz, Eva A1 - Appelhoff, Stefan A1 - Arnatkeviciute, Aurina A1 - Atay, Selim Melvin A1 - Auer, Tibor A1 - Baracchini, Giulia A1 - Bayer, Johanna M M A1 - Beauvais, Michael J S A1 - Bijsterbosch, Janine D A1 - Bilgin, Isil P A1 - Bollmann, Saskia A1 - Bollmann, Steffen A1 - Botvinik-Nezer, Rotem A1 - Bright, Molly G A1 - Calhoun, Vince D A1 - Chen, Xiao A1 - Chopra, Sidhant A1 - Chuan-Peng, Hu A1 - Close, Thomas G A1 - Cookson, Savannah L A1 - Craddock, R Cameron A1 - De La Vega, Alejandro A1 - De Leener, Benjamin A1 - Demeter, Damion V A1 - Di Maio, Paola A1 - Dickie, Erin W A1 - Eickhoff, Simon B A1 - Esteban, Oscar A1 - Finc, Karolina A1 - Frigo, Matteo A1 - Ganesan, Saampras A1 - Ganz, Melanie A1 - Garner, Kelly G A1 - Garza-Villarreal, Eduardo A A1 - Gonzalez-Escamilla, Gabriel A1 - Goswami, Rohit A1 - Griffiths, John D A1 - Grootswagers, Tijl A1 - Guay, Samuel A1 - Guest, Olivia A1 - Handwerker, Daniel A A1 - Herholz, Peer A1 - Heuer, Katja A1 - Huijser, Dorien C A1 - Iacovella, Vittorio A1 - Joseph, Michael J E A1 - Karakuzu, Agah A1 - Keator, David B A1 - Kobeleva, Xenia A1 - Kumar, Manoj A1 - Laird, Angela R A1 - Larson-Prior, Linda J A1 - Lautarescu, Alexandra A1 - Lazari, Alberto A1 - Legarreta, Jon Haitz A1 - Li, Xue-Ying A1 - Lv, Jinglei A1 - Mansour L., Sina A1 - Meunier, David A1 - Moraczewski, Dustin A1 - Nandi, Tulika A1 - Nastase, Samuel A A1 - Nau, Matthias A1 - Noble, Stephanie A1 - Norgaard, Martin A1 - Obungoloch, Johnes A1 - Oostenveld, Robert A1 - Orchard, Edwina R A1 - Pinho, Ana Luísa A1 - Poldrack, Russell A A1 - Qiu, Anqi A1 - Raamana, Pradeep Reddy A1 - Rokem, Ariel A1 - Rutherford, Saige A1 - Sharan, Malvika A1 - Shaw, Thomas B A1 - Syeda, Warda T A1 - Testerman, Meghan M A1 - Toro, Roberto A1 - Valk, Sofie L A1 - Van Den Bossche, Sofie A1 - Varoquaux, Gaël A1 - Váša, František A1 - Veldsman, Michele A1 - Vohryzek, Jakub A1 - Wagner, Adina S A1 - Walsh, Reubs J A1 - White, Tonya A1 - Wong, Fu-Te A1 - Xie, Xihe A1 - Yan, Chao-Gan A1 - Yang, Yu-Fang A1 - Yee, Yohan A1 - Zanitti, Gaston E A1 - Van Gulick, Ana E A1 - Duff, Eugene A1 - Maumet, Camille T1 - Centering inclusivity in the design of online conferences—An OHBM–Open Science perspective JF - GigaScience N2 - As the global health crisis unfolded, many academic conferences moved online in 2020. This move has been hailed as a positive step towards inclusivity in its attenuation of economic, physical, and legal barriers and effectively enabled many individuals from groups that have traditionally been underrepresented to join and participate. A number of studies have outlined how moving online made it possible to gather a more global community and has increased opportunities for individuals with various constraints, e.g., caregiving responsibilities. Yet, the mere existence of online conferences is no guarantee that everyone can attend and participate meaningfully. In fact, many elements of an online conference are still significant barriers to truly diverse participation: the tools used can be inaccessible for some individuals; the scheduling choices can favour some geographical locations; the set-up of the conference can provide more visibility to well-established researchers and reduce opportunities for early-career researchers. While acknowledging the benefits of an online setting, especially for individuals who have traditionally been underrepresented or excluded, we recognize that fostering social justice requires inclusivity to actively be centered in every aspect of online conference design. Here, we draw from the literature and from our own experiences to identify practices that purposefully encourage a diverse community to attend, participate in, and lead online conferences. Reflecting on how to design more inclusive online events is especially important as multiple scientific organizations have announced that they will continue offering an online version of their event when in-person conferences can resume. KW - online conferences KW - diversity KW - inclusivity KW - open science KW - collaborative events Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-371574 VL - 10 ER -