Journal article
TNFR1-dependent cell death drives inflammation in Sharpin-deficient mice
eLife | Published : 2014
DOI: 10.7554/eLife.03464
Open access
Abstract
SHARPIN regulates immune signaling and contributes to full transcriptional activity and prevention of cell death in response to TNF in vitro. The inactivating mouse Sharpin cpdm mutation causes TNF-dependent multi-organ inflammation, characterized by dermatitis, liver inflammation, splenomegaly, and loss of Peyer's patches. TNF-dependent cell death has been proposed to cause the inflammatory phenotype and consistent with this we show Tnfr1, but not Tnfr2, deficiency suppresses the phenotype (and it does so more efficiently than Il1r1 loss). TNFR1-induced apoptosis can proceed through caspase-8 and BID, but reduction in or loss of these players generally did not suppress inflammation, althoug..
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Awarded by European Commission
Funding Acknowledgements
National Health and Medical Research Council 1025594 John Silke Australian Cancer Research Foundation James M Murphy Thomas William Francis and Violet Coles Trust Fund James A Rickard, John Silke State Government of Victoria Operational Infrastructure Support (OIS) James A Rickard, Holly Anderton, Nima Etemadi, Ueli Nachbur, Najoua Lalaoui, Kate E Lawlor, Hannah Vanyai, Cathrine Hall, Aleks Bankovacki, Jason Corbin, James M Murphy, Warren S Alexander, Anne K Voss, David L Vaux, John Silke National Institutes of Health OD012198 William J Kaiser National Health and Medical Research Council 1046984 John Silke National Health and Medical Research Council 1046010 John Silke National Health and Medical Research Council 1051210 Kate E Lawlor National Health and Medical Research Council 1057905 James M Murphy, John Silke National Health and Medical Research Council 575512 Anne K Voss National Health and Medical Research Council 541901 John Silke National Health and Medical Research Council 1058344 Warren S Alexander National Institutes of Health GM112547 Edward S Mocarski Wellcome Trust 096831/Z/11/Z Henning Walczak European Research Council 294880 Henning Walczak National Health and Medical Research Council 361646 James A Rickard, Holly Anderton, Nima Etemadi, Ueli Nachbur, Najoua Lalaoui, Kate E Lawlor, Cathrine Hall, Aleks Bankovacki, Jason Corbin, James M Murphy, Warren S Alexander, Anne K Voss, David L Vaux, John Silke National Health and Medical Research Council 1016647 Warren S Alexander National Health and Medical Research Council 461221 David L Vaux