TY  - JOUR
A1  - Gewies, Andreas
A1  - Gorka, Oliver
A1  - Bergmann, Hanna
A1  - Pechloff, Konstanze
A1  - Petermann, Franziska
A1  - Jeltsch, Katharina M.
A1  - Rudelius, Martina
A1  - Kriegsmann, Mark
A1  - Weichert, Wilko
A1  - Horsch, Marion
A1  - Beckers, Johannes
A1  - Wurst, Wolfgang
A1  - Heikenwalder, Mathias
A1  - Korn, Thomas
A1  - Heissmeyer, Vigo
A1  - Ruland, Juergen
T1  - Uncoupling Malt1 Threshold Function from Paracaspase Activity Results in Destructive Autoimmune Inflammation
JF  - Cell Reports
N2  - The paracaspase Malt1 is a central regulator of antigen receptor signaling that is frequently mutated in human lymphoma. As a scaffold, it assembles protein complexes for NF-kappa B activation, and its proteolytic domain cleaves negative NF-kappa B regulators for signal enforcement. Still, the physiological functions of Malt1-protease are unknown. We demonstrate that targeted Malt1-paracaspase inactivation induces a lethal inflammatory syndrome with lymphocyte-dependent neurodegeneration in vivo. Paracaspase activity is essential for regulatory T cell (Treg) and innate-like B cell development, but it is largely dispensable for overcoming Malt1-dependent thresholds for lymphocyte activation. In addition to NF-kappa B inhibitors, Malt1 cleaves an entire set of mRNA stability regulators, including Roquin-1, Roquin-2, and Regnase-1, and paracaspase inactivation results in excessive interferon gamma (IFN gamma) production by effector lymphocytes that drive pathology. Together, our results reveal distinct threshold and modulatory functions of Malt1 that differentially control lymphocyte differentiation and activation pathways and demonstrate that selective paracaspase blockage skews systemic immunity toward destructive autoinflammation.
KW  - helper T-cells
KW  - combined immunodeficiency
KW  - messenger RNA
KW  - roquin
KW  - mice
KW  - NF-KAPPA-B
KW  - lymphoid-tissue
KW  - activation
KW  - cleavage
KW  - mutations
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-114627
VL  - 9
IS  - 4
ER  - 
TY  - JOUR
A1  - Le Provost, Gaëtane
A1  - Thiele, Jan
A1  - Westphal, Catrin
A1  - Penone, Caterina
A1  - Allan, Eric
A1  - Neyret, Margot
A1  - van der Plas, Fons
A1  - Ayasse, Manfred
A1  - Bardgett, Richard D.
A1  - Birkhofer, Klaus
A1  - Boch, Steffen
A1  - Bonkowski, Michael
A1  - Buscot, Francois
A1  - Feldhaar, Heike
A1  - Gaulton, Rachel
A1  - Goldmann, Kezia
A1  - Gossner, Martin M.
A1  - Klaus, Valentin H.
A1  - Kleinebecker, Till
A1  - Krauss, Jochen
A1  - Renner, Swen
A1  - Scherreiks, Pascal
A1  - Sikorski, Johannes
A1  - Baulechner, Dennis
A1  - Blüthgen, Nico
A1  - Bolliger, Ralph
A1  - Börschig, Carmen
A1  - Busch, Verena
A1  - Chisté, Melanie
A1  - Fiore-Donno, Anna Maria
A1  - Fischer, Markus
A1  - Arndt, Hartmut
A1  - Hoelzel, Norbert
A1  - John, Katharina
A1  - Jung, Kirsten
A1  - Lange, Markus
A1  - Marzini, Carlo
A1  - Overmann, Jörg
A1  - Paŝalić, Esther
A1  - Perović, David J.
A1  - Prati, Daniel
A1  - Schäfer, Deborah
A1  - Schöning, Ingo
A1  - Schrumpf, Marion
A1  - Sonnemann, Ilja
A1  - Steffan-Dewenter, Ingolf
A1  - Tschapka, Marco
A1  - Türke, Manfred
A1  - Vogt, Juliane
A1  - Wehner, Katja
A1  - Weiner, Christiane
A1  - Weisser, Wolfgang
A1  - Wells, Konstans
A1  - Werner, Michael
A1  - Wolters, Volkmar
A1  - Wubet, Tesfaye
A1  - Wurst, Susanne
A1  - Zaitsev, Andrey S.
A1  - Manning, Peter
T1  - Contrasting responses of above- and belowground diversity to multiple components of land-use intensity
JF  - Nature Communications
N2  - Land-use intensification is a major driver of biodiversity loss. However, understanding how different components of land use drive biodiversity loss requires the investigation of multiple trophic levels across spatial scales. Using data from 150 agricultural grasslands in central Europe, we assess the influence of multiple components of local- and landscape-level land use on more than 4,000 above- and belowground taxa, spanning 20 trophic groups. Plot-level land-use intensity is strongly and negatively associated with aboveground trophic groups, but positively or not associated with belowground trophic groups. Meanwhile, both above- and belowground trophic groups respond to landscape-level land use, but to different drivers: aboveground diversity of grasslands is promoted by diverse surrounding land-cover, while belowground diversity is positively related to a high permanent forest cover in the surrounding landscape. These results highlight a role of landscape-level land use in shaping belowground communities, and suggest that revised agroecosystem management strategies are needed to conserve whole-ecosystem biodiversity.
KW  - biodiversity
KW  - community ecology
KW  - grassland ecology
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-371552
VL  - 12
ER  -