TRAF2 regulates TNF and NF-κB signalling to suppress apoptosis and skin inflammation independently of Sphingosine kinase-1
- Walter and Eliza Hall Institute of Medical Research, Australia
- Monash University, Australia
- Cornell University, United States
- SA Pathology, Australia
- University of Zurich, Switzerland
- Olivia Newton-John Cancer Research Institute, Australia
Abstract
TRAF2 is a component of TNF superfamily signalling complexes and plays an essential role in the regulation and homeostasis of immune cells. TRAF2 deficient mice die around birth, therefore its role in adult tissues is not well-explored. Furthermore, the role of the TRAF2 RING is controversial. It has been claimed that the atypical TRAF2 RING cannot function as a ubiquitin E3 ligase but counterclaimed that TRAF2 RING requires a co-factor, sphingosine-1-phosphate, that is generated by the enzyme sphingosine kinase-1, to function as an E3 ligase. Keratinocyte specific deletion of Traf2, but not Sphk1 deficiency, disrupted TNF mediated NF-κB and MAP kinase signalling and caused epidermal hyperplasia and psoriatic skin inflammation. This inflammation was driven by TNF, cell death, non-canonical NF-κB and the adaptive immune system and might therefore represent a clinically relevant model of psoriasis. TRAF2 therefore has essential tissue specific functions that do not overlap with those of Sphk1.
Article and author information
Author details
Reviewing Editor
- Ivan Dikic, Goethe University Medical School, Germany
Ethics
Animal experimentation: Mice were maintained at the Walter and Eliza Hall Institute (WEHI) under the approval of WEHI ethics committee and Institute guidelines. All procedures were specifcally approved under WEHI Ethics Project Number 2011.013 and 2014.015.
Version history
- Received: August 4, 2015
- Accepted: December 21, 2015
- Accepted Manuscript published: December 23, 2015 (version 1)
- Version of Record published: February 16, 2016 (version 2)
- Version of Record updated: June 27, 2017 (version 3)
Copyright
© 2015, Etemadi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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TRAF2 regulates TNF and NF-κB signalling to suppress apoptosis and skin inflammation independently of Sphingosine kinase-1
eLife 4:e10592.
https://doi.org/10.7554/eLife.10592
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