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Zsófia Agnes Bittner, Xiao Liu, Maria Mateo Tortola, Ana Tapia-Abellán, Sangeetha Shankar, Liudmila Andreeva, Matthew Mangan, Marianne Spalinger, Hubert Kalbacher, Peter Düwell, Marta Lovotti, Karlotta Bosch, Sabine Dickhöfer, Ana Marcu, Stefan Stevanović, Franziska Herster, Yamel Cardona Gloria, Tzu-Hsuan Chang, Francesca Bork, Carsten L. Greve, Markus W. Löffler, Olaf-Oliver Wolz, Nadine A. Schilling, Jasmin B. Kümmerle-Deschner, Samuel Wagner, Anita Delor, Bodo Grimbacher, Oliver Hantschel, Michael Scharl, Hao Wu, Eicke Latz, Alexander N.R. Weber
Bittner et al. discovered that direct phosphorylation of the inflammasome sensor NLRP3, by the well-established drug target Bruton’s tyrosine kinase (BTK), promotes inflammasome assembly and boosts IL-1β release. NLRP3 phosphorylation by BTK may thus represent a novel target for therapeutic intervention in inflammation.
Brief Definitive Report
Chia-Hao Lin, Mei-Chi Chen, Ling-Li Lin, David A. Christian, Booki Min, Christopher A. Hunter, Li-Fan Lu
IL-27 is a pleiotropic cytokine that plays important immunological roles in many disease settings. This study demonstrates that in addition to its known regulatory properties in preventing immune hyperactivity, gut epithelial IL-27 confers barrier immunity through promoting a distinct intraepithelial lymphocyte population.
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Jakob Kreye, Sukhvir K. Wright, Adriana van Casteren, Laura Stöffler, Marie-Luise Machule, S. Momsen Reincke, Marc Nikolaus, Scott van Hoof, Elisa Sanchez-Sendin, Marie A. Homeyer, César Cordero Gómez, Hans-Christian Kornau, Dietmar Schmitz, Angela M. Kaindl, Philipp Boehm-Sturm, Susanne Mueller, Max A. Wilson, Manoj A. Upadhya, Divya R. Dhangar, Stuart Greenhill, Gavin Woodhall, Paul Turko, Imre Vida, Craig C. Garner, Jonathan Wickel, Christian Geis, Yuko Fukata, Masaki Fukata, Harald Prüss
Kreye et al. report the isolation of human monoclonal GABAAR antibodies and demonstrate their direct pathogenicity in vitro and in vivo independent of Fc-mediated effector functions. These encephalitis patient-derived antibodies explain the clinical phenotype and can expedite the development of selective immunotherapies.
Brief Definitive Report
Claire Pujol, Anne Legrand et al.
This study characterizes a Cyp2u1−/− mouse model and connects neurodevelopmental deficits to mitochondrial dysfunctions and folate, which could be prevented by folate supplementation in a mouse model. It also validates biochemical and imaging biomarkers in SPG56 patients, which are critical to allow drug development.
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Vishwas Mishra, Avipsa Bose, Shashi Kiran, Sanghita Banerjee, Idrees A. Shah, Pooja Chaukimath, Mudasir M. Reshi, Swarna Srinivas, Anaxee Barman, Sandhya S. Visweswariah
A novel preclinical mouse model harboring an activating mutation in Gucy2c demonstrates features seen in patients with familial GUCY2C diarrhea syndrome. Fecal microbiome changes and colonic gene expression identify cell intrinsic and extrinsic roles of cGMP in gut inflammation.
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Chris D. Hermann, Benjamin Schoeps, Celina Eckfeld, Enkhtsetseg Munkhbaatar, Lukas Kniep, Olga Prokopchuk, Nils Wirges, Katja Steiger, Daniel Häußler, Percy Knolle, Emily Poulton, Rama Khokha, Barbara T. Grünwald, Ihsan Ekin Demir, Achim Krüger
Hermann et al. reveal a lifestyle-independent sex disparity in liver metastasis and survival of pancreatic cancer caused by TIMP1. Increased TIMP1 expression in males predicts liver metastasis in various cancer entities. Such insight into the basis of sex differences substantiates the necessity of considering sex in cancer medicine.
Article
Annika Hausmann, Boas Felmy, Leo Kunz, Sanne Kroon, Dorothée Lisa Berthold, Giverny Ganz, Ioana Sandu, Toshihiro Nakamura, Nathan Sébastien Zangger, Yang Zhang, Tamas Dolowschiak, Stefan Alexander Fattinger, Markus Furter, Anna Angelika Müller-Hauser, Manja Barthel, Katerina Vlantis, Laurens Wachsmuth, Jan Kisielow, Luigi Tortola, Danijela Heide, Mathias Heikenwälder, Annette Oxenius, Manfred Kopf, Timm Schroeder, Manolis Pasparakis, Mikael Erik Sellin, Wolf-Dietrich Hardt
Hausmann et al. describe a sentinel intercrypt macrophage population in the intestine, which detects Gram-negative microbes breaching the epithelial barrier and elicits epithelial NF-κB signaling in neighboring crypts. The tunability of this crypt-scale response allows the induction of appropriately scaled defenses according to the localization and intensity of microbial triggers.

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Current Issue
Volume 218,
Issue 9,
September 6, 2021
Reviews & Opinions
Insights
Anna E. Beaudin
Pieters et al. establish a novel mouse model of MCL driven by overexpression of cyclin D2 and identify fetal-derived B1a cells as putative cell of origin for MCL.
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