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Series GSE55360 Query DataSets for GSE55360
Status Public on Oct 27, 2014
Title Uncoupling Malt1 threshold function from paracaspase activity results in destructive autoimmune inflammation
Organism Mus musculus
Experiment type Expression profiling by array
Summary 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-kB activation, and its proteolytic domain cleaves negative NF-kB 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 and innate-like B-cell development, but it is largely dispensable for overcoming Malt1-dependent thresholds for lymphocyte activation. In addition to NF-kB inhibitors, Malt1 cleaves an entire set of mRNA stability regulators, including Roquin-1, Roquin-2 and Regnase-1, and paracaspase inactivation results in excessive IFNγ production by effector lymphocytes that drives 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 towards destructive autoinflammation.

Overall design Total RNA obtained from T cells with (1h and 4 h) and without stimulation, 3 biological replicates, 3 genotypes (Malt+/-, Malt-/-, MaltPM/-)
Contributor(s) Johannes B, Marion H
Citation(s) 25456129
Submission date Feb 26, 2014
Last update date Jun 14, 2018
Contact name Martin Irmler
Organization name Helmholtz Zentrum München GmbH
Department Institute of Experimental Genetics
Lab Gene Regulation & Epigenetics
Street address Ingolstaedter Landstrasse 1
City Neuherberg
State/province Bayern
ZIP/Postal code 85764
Country Germany
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (36)
GSM1334686 E3 het 0h
GSM1334687 E4 het 0h
GSM1334688 E5 het 0h
BioProject PRJNA239410

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE55360_RAW.tar 3.1 Mb (http)(custom) TAR
GSE55360_non-normalized.txt.gz 5.4 Mb (ftp)(http) TXT
Processed data included within Sample table
Raw data are available on Series record

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