|
Status |
Public on Jun 10, 2015 |
Title |
Cancerous inhibitor of Protein Phosphatase 2A is a novel cell-autonomous regulator governing both T-and B-cell activation in vivo |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
|
Summary |
The generation of optimal immune response requires combined activation of both T- and B-cells. Here, we demonstrate that the cancerous inhibitor of protein phosphatase 2A (CIP2A) is a novel factor that governs activation of both T- and B-cells in vivo. Upon ovalbumin challenge, CIP2A-deficient (CIP2AHOZ) mice show impaired immune response. Furthermore, CIP2AHOZ mice had impaired clearance of Listeria Monocytogenesis (L.m.) infection, combined with decreased numbers of CD8+ T-cells and IFN-γ secretion. In an ovalbumin model of allergic asthma, CIP2AHOZ B-cells were impaired in IgE and IgG secretion, despite of normal Th2 differentiation and unaffected numbers of inflammatory cells or cytokines in bronchoalveolar lavage. Importantly, the cell-autonomous effect of CIP2A deficiency for both T- and B-cell activation was confirmed by in vitro assays. During the T-cell activation CIP2A, was shown to promote expression of ETS-1, whereas in B-cells CIP2A loss resulted in inhibition of MYC-mediated gene expression. Together these results identify CIP2A as a novel cell-autonomous regulator governing both T- and B-cell activation in vivo. They also identify CIP2AHOZ as a novel murine model for investigation of impaired immune response and allergic asthma.
|
|
|
Overall design |
Total RNA obtained from 4 male mutant mice was compared to 4 wild type controls.
|
|
|
Contributor(s) |
Beckers J, Horsch M |
Citation(s) |
27100879 |
|
Submission date |
Apr 01, 2014 |
Last update date |
May 28, 2020 |
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 (8)
|
|
Relations |
BioProject |
PRJNA243188 |