TRAF2 regulates TNF and NF-κB signalling to suppress apoptosis and skin inflammation independently of Sphingosine kinase 1.

2015-12-23

Etemadi, Nima

Chopin, Michael

Anderton, Holly

Tanzer, Maria C

Rickard, James A

Abeysekera, Waruni

Hall, Cathrine

Spall, Sukhdeep K

Wang, Bing

Xiong, Yuquan

Hla, Timothy

Pitson, Stuart M

Bonder, Claudine S

Wong, Wendy Wei-Lynn

Ernst, Matthias

Smyth, Gordon K

Vaux, David L

Nutt, Stephen L

Nachbur, Ueli

Silke, John

NF-kB

TNF

apoptosis

biochemistry

immunology

inflammation

mouse

psoriasis

Journal Article

0000-0002-7137-1373

0000-0001-9221-2892

0000-0002-0020-6637

0000-0002-6399-1177

10.7554/eLife.10592

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.

link

eLife 2015-12-23; 4

eLife