Impact of loss of NF-κB1, NF-κB2 or c-REL on SLE-like autoimmune disease and lymphadenopathy in Faslpr/lpr mutant mice

JT Low; P Hughes; A Lin; U Siebenlist; R Jain; K Yaprianto; DHD Gray; S Gerondakis; A Strasser; LA O'Reilly

Journal article

Impact of loss of NF-κB1, NF-κB2 or c-REL on SLE-like autoimmune disease and lymphadenopathy in Faslpr/lpr mutant mice

JT Low, P Hughes, A Lin, U Siebenlist, R Jain, K Yaprianto, DHD Gray, S Gerondakis, A Strasser, LA O'Reilly

Immunology and Cell Biology | Published : 2016

DOI: 10.1038/icb.2015.66

Abstract

Defects in apoptosis can cause autoimmune disease. Loss-of-function mutations in the 'death receptor' FAS impair the deletion of autoreactive lymphocytes in the periphery, leading to progressive lymphadenopathy and systemic lupus erythematosus-like autoimmune disease in mice (Faslpr/lpr (mice homozygous for the lymphoproliferation inducing spontaneous mutation)) and humans. The REL/nuclear factor-κB (NF-κB) transcription factors regulate a broad range of immune effector functions and are also implicated in various autoimmune diseases. We generated compound mutant mice to investigate the individual functions of the NF-κB family members NF-κB1, NF-κB2 and c-REL in the various autoimmune pathol..

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University of Melbourne Researchers

Peter Hughes Author

Reema Jain Author

Daniel Gray Author

Andreas Strasser Author

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Grants

Awarded by National Institute of Allergy and Infectious Diseases

Funding Acknowledgements

We thank G Siciliano and K Hughes for animal care; J Corbin for automated blood analysis; B Helbert, C Young and Karen Mackwell for genotyping; and E Tsui, V Babo, K Weston and all histology staff for preparation of histological sections. This work was supported by fellowships and grants from the NHMRC, Canberra, programme 1016701, fellowships; 637353 (DHDG), 1090236 (DHDG), 1020363 (AS) and project grants; 1046010 (AS), 1009145 (LAO'R), 1049724 (DHDG), Australian Postgraduate Award (JTL) and an NHMRC infrastructure grant; Independent Research Institutes Infrastructure Support Scheme Grant 361646, the Victorian State Government (OIS grant), the Leukemia and Lymphoma Society (SCOR grant 7413 and 7001-13) and the JDRF/NHMRC 466658 (AS). This research was also supported in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health (US).