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

Nima Etemadi; Michael Chopin; Holly Anderton; Maria C Tanzer; James A Rickard; Waruni Abeysekera; Cathrine M 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

doi:10.7554/eLife.10592

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

Nima Etemadi, Michael Chopin, Holly Anderton, Maria C Tanzer, James A Rickard, Waruni Abeysekera, Cathrine M 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

Epidemiology and Preventive Medicine Alfred Hospital

Research output: Contribution to journal › Article › Research › peer-review

83 Citations (Scopus)

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.

Original language	English
Article number	e10592
Number of pages	27
Journal	eLife
Volume	4
DOIs	https://doi.org/10.7554/eLife.10592
Publication status	Published - 23 Dec 2015

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10.7554/eLife.10592

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Etemadi, N., Chopin, M., Anderton, H., Tanzer, M. C., Rickard, J. A., Abeysekera, W., Hall, C. M., Spall, S. K., Wang, B., Xiong, Y., Hla, T., Pitson, S. M., Bonder, C. S., Wong, W. W. L., Ernst, M., Smyth, G. K., Vaux, D. L., Nutt, S. L., Nachbur, U., & Silke, J. (2015). TRAF2 regulates TNF and NF-κB signalling to suppress apoptosis and skin inflammation independently of sphingosine kinase. eLife, 4, Article e10592. https://doi.org/10.7554/eLife.10592

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title = "TRAF2 regulates TNF and NF-κB signalling to suppress apoptosis and skin inflammation independently of sphingosine kinase",

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.",

author = "Nima Etemadi and Michael Chopin and Holly Anderton and Tanzer, {Maria C} and Rickard, {James A} and Waruni Abeysekera and Hall, {Cathrine M} and Spall, {Sukhdeep K} and Bing Wang and Yuquan Xiong and Timothy Hla and Pitson, {Stuart M} and Bonder, {Claudine S} and Wong, {Wendy Wei Lynn} and Matthias Ernst and Smyth, {Gordon K} and Vaux, {David L.} and Nutt, {Stephen L} and Ueli Nachbur and John Silke",

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Etemadi, N, Chopin, M, Anderton, H, Tanzer, MC, Rickard, JA, Abeysekera, W, Hall, CM, Spall, SK, Wang, B, Xiong, Y, Hla, T, Pitson, SM, Bonder, CS, Wong, WWL, Ernst, M, Smyth, GK, Vaux, DL, Nutt, SL, Nachbur, U & Silke, J 2015, 'TRAF2 regulates TNF and NF-κB signalling to suppress apoptosis and skin inflammation independently of sphingosine kinase', eLife, vol. 4, e10592. https://doi.org/10.7554/eLife.10592

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AU - Abeysekera, Waruni

AU - Hall, Cathrine M

AU - Spall, Sukhdeep K

AU - Wang, Bing

AU - Xiong, Yuquan

AU - Hla, Timothy

AU - Pitson, Stuart M

AU - Bonder, Claudine S

AU - Wong, Wendy Wei Lynn

AU - Ernst, Matthias

AU - Smyth, Gordon K

AU - Vaux, David L.

AU - Nutt, Stephen L

AU - Nachbur, Ueli

AU - Silke, John

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

Abstract

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Erratum: Correction: TRAF2 regulates TNF and NF-κB signalling to suppress apoptosis and skin inflammation independently of Sphingosine kinase 1 (eLife (2015) 4 PII: e29849)

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