TRAF2 regulates TNF and NF-κB signalling to suppress apoptosis and skin inflammation independently of Sphingosine kinase 1
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 ha...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2015-12-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/10592 |
| _version_ | 1811201071730655232 |
|---|---|
| author | Nima Etemadi Michael Chopin Holly Anderton Maria C Tanzer James A Rickard Waruni Abeysekera Cathrine Hall Sukhdeep K Spall Bing Wang Yuquan Xiong Timothy Hla Stuart M Pitson Claudine S Bonder Wendy Wei-Lynn Wong Matthias Ernst Gordon K Smyth David L Vaux Stephen L Nutt Ueli Nachbur John Silke |
| author_facet | Nima Etemadi Michael Chopin Holly Anderton Maria C Tanzer James A Rickard Waruni Abeysekera Cathrine Hall Sukhdeep K Spall Bing Wang Yuquan Xiong Timothy Hla Stuart M Pitson Claudine S Bonder Wendy Wei-Lynn Wong Matthias Ernst Gordon K Smyth David L Vaux Stephen L Nutt Ueli Nachbur John Silke |
| author_sort | Nima Etemadi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T02:14:45Z |
| format | Article |
| id | doaj.art-9cd7f75afca343d2bcba08b6b036730f |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:14:45Z |
| publishDate | 2015-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-9cd7f75afca343d2bcba08b6b036730f2022-12-22T03:52:17ZengeLife Sciences Publications LtdeLife2050-084X2015-12-01410.7554/eLife.10592TRAF2 regulates TNF and NF-κB signalling to suppress apoptosis and skin inflammation independently of Sphingosine kinase 1Nima Etemadi0https://orcid.org/0000-0002-7137-1373Michael Chopin1Holly Anderton2Maria C Tanzer3James A Rickard4Waruni Abeysekera5Cathrine Hall6Sukhdeep K Spall7Bing Wang8Yuquan Xiong9Timothy Hla10Stuart M Pitson11Claudine S Bonder12Wendy Wei-Lynn Wong13Matthias Ernst14Gordon K Smyth15https://orcid.org/0000-0001-9221-2892David L Vaux16Stephen L Nutt17https://orcid.org/0000-0002-0020-6637Ueli Nachbur18John Silke19Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, Australia; Olivia Newton-John Cancer Research Institute, Heidelberg, Australia; School of Cancer Medicine, La Trobe University, Heidelberg, AustraliaWalter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, AustraliaWalter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, AustraliaWalter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, AustraliaWalter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, AustraliaWalter and Eliza Hall Institute of Medical Research, Parkville, AustraliaWalter and Eliza Hall Institute of Medical Research, Parkville, AustraliaWalter and Eliza Hall Institute of Medical Research, Parkville, AustraliaCenter for Cardiovascular Research and Education in Therapeutics, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, AustraliaCenter for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York, United StatesCenter for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York, United StatesCentre for Cancer Biology, SA Pathology, Adelaide, AustraliaCentre for Cancer Biology, SA Pathology, Adelaide, AustraliaInstitute of Experimental Immunology, University of Zurich, Zurich, SwitzerlandOlivia Newton-John Cancer Research Institute, Heidelberg, Australia; School of Cancer Medicine, La Trobe University, Heidelberg, AustraliaWalter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Mathematics and Statistics, University of Melbourne, Parkville, AustraliaWalter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, AustraliaWalter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, AustraliaWalter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, AustraliaWalter and Eliza Hall Institute of Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Parkville, AustraliaTRAF2 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.https://elifesciences.org/articles/10592TNFapoptosisinflammationNF-kBpsoriasis |
| spellingShingle | Nima Etemadi Michael Chopin Holly Anderton Maria C Tanzer James A Rickard Waruni Abeysekera Cathrine Hall Sukhdeep K Spall Bing Wang Yuquan Xiong Timothy Hla Stuart M Pitson Claudine S Bonder Wendy Wei-Lynn Wong Matthias Ernst Gordon K Smyth David L Vaux Stephen L Nutt Ueli Nachbur John Silke TRAF2 regulates TNF and NF-κB signalling to suppress apoptosis and skin inflammation independently of Sphingosine kinase 1 eLife TNF apoptosis inflammation NF-kB psoriasis |
| title | TRAF2 regulates TNF and NF-κB signalling to suppress apoptosis and skin inflammation independently of Sphingosine kinase 1 |
| title_full | TRAF2 regulates TNF and NF-κB signalling to suppress apoptosis and skin inflammation independently of Sphingosine kinase 1 |
| title_fullStr | TRAF2 regulates TNF and NF-κB signalling to suppress apoptosis and skin inflammation independently of Sphingosine kinase 1 |
| title_full_unstemmed | TRAF2 regulates TNF and NF-κB signalling to suppress apoptosis and skin inflammation independently of Sphingosine kinase 1 |
| title_short | TRAF2 regulates TNF and NF-κB signalling to suppress apoptosis and skin inflammation independently of Sphingosine kinase 1 |
| title_sort | traf2 regulates tnf and nf κb signalling to suppress apoptosis and skin inflammation independently of sphingosine kinase 1 |
| topic | TNF apoptosis inflammation NF-kB psoriasis |
| url | https://elifesciences.org/articles/10592 |
| work_keys_str_mv | AT nimaetemadi traf2regulatestnfandnfkbsignallingtosuppressapoptosisandskininflammationindependentlyofsphingosinekinase1 AT michaelchopin traf2regulatestnfandnfkbsignallingtosuppressapoptosisandskininflammationindependentlyofsphingosinekinase1 AT hollyanderton traf2regulatestnfandnfkbsignallingtosuppressapoptosisandskininflammationindependentlyofsphingosinekinase1 AT mariactanzer traf2regulatestnfandnfkbsignallingtosuppressapoptosisandskininflammationindependentlyofsphingosinekinase1 AT jamesarickard traf2regulatestnfandnfkbsignallingtosuppressapoptosisandskininflammationindependentlyofsphingosinekinase1 AT waruniabeysekera traf2regulatestnfandnfkbsignallingtosuppressapoptosisandskininflammationindependentlyofsphingosinekinase1 AT cathrinehall traf2regulatestnfandnfkbsignallingtosuppressapoptosisandskininflammationindependentlyofsphingosinekinase1 AT sukhdeepkspall traf2regulatestnfandnfkbsignallingtosuppressapoptosisandskininflammationindependentlyofsphingosinekinase1 AT bingwang traf2regulatestnfandnfkbsignallingtosuppressapoptosisandskininflammationindependentlyofsphingosinekinase1 AT yuquanxiong traf2regulatestnfandnfkbsignallingtosuppressapoptosisandskininflammationindependentlyofsphingosinekinase1 AT timothyhla traf2regulatestnfandnfkbsignallingtosuppressapoptosisandskininflammationindependentlyofsphingosinekinase1 AT stuartmpitson traf2regulatestnfandnfkbsignallingtosuppressapoptosisandskininflammationindependentlyofsphingosinekinase1 AT claudinesbonder traf2regulatestnfandnfkbsignallingtosuppressapoptosisandskininflammationindependentlyofsphingosinekinase1 AT wendyweilynnwong traf2regulatestnfandnfkbsignallingtosuppressapoptosisandskininflammationindependentlyofsphingosinekinase1 AT matthiasernst traf2regulatestnfandnfkbsignallingtosuppressapoptosisandskininflammationindependentlyofsphingosinekinase1 AT gordonksmyth traf2regulatestnfandnfkbsignallingtosuppressapoptosisandskininflammationindependentlyofsphingosinekinase1 AT davidlvaux traf2regulatestnfandnfkbsignallingtosuppressapoptosisandskininflammationindependentlyofsphingosinekinase1 AT stephenlnutt traf2regulatestnfandnfkbsignallingtosuppressapoptosisandskininflammationindependentlyofsphingosinekinase1 AT uelinachbur traf2regulatestnfandnfkbsignallingtosuppressapoptosisandskininflammationindependentlyofsphingosinekinase1 AT johnsilke traf2regulatestnfandnfkbsignallingtosuppressapoptosisandskininflammationindependentlyofsphingosinekinase1 |