LUBAC prevents lethal dermatitis by inhibiting cell death induced by TNF, TRAIL and CD95L

N/ACitations
Citations of this article
100Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

The linear ubiquitin chain assembly complex (LUBAC), composed of HOIP, HOIL-1 and SHARPIN, is required for optimal TNF-mediated gene activation and to prevent cell death induced by TNF. Here, we demonstrate that keratinocyte-specific deletion of HOIP or HOIL-1 (E-KO) results in severe dermatitis causing postnatal lethality. We provide genetic and pharmacological evidence that the postnatal lethal dermatitis in HoipE-KO and Hoil-1E-KO mice is caused by TNFR1-induced, caspase-8-mediated apoptosis that occurs independently of the kinase activity of RIPK1. In the absence of TNFR1, however, dermatitis develops in adulthood, triggered by RIPK1-kinase-activity-dependent apoptosis and necroptosis. Strikingly, TRAIL or CD95L can redundantly induce this disease-causing cell death, as combined loss of their respective receptors is required to prevent TNFR1-independent dermatitis. These findings may have implications for the treatment of patients with mutations that perturb linear ubiquitination and potentially also for patients with inflammation-associated disorders that are refractory to inhibition of TNF alone.

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Taraborrelli, L., Peltzer, N., Montinaro, A., Kupka, S., Rieser, E., Hartwig, T., … Walczak, H. (2018). LUBAC prevents lethal dermatitis by inhibiting cell death induced by TNF, TRAIL and CD95L. Nature Communications, 9(1). https://doi.org/10.1038/s41467-018-06155-8

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 37

64%

Researcher 15

26%

Professor / Associate Prof. 3

5%

Lecturer / Post doc 3

5%

Readers' Discipline

Tooltip

Biochemistry, Genetics and Molecular Bi... 34

57%

Agricultural and Biological Sciences 11

18%

Immunology and Microbiology 8

13%

Medicine and Dentistry 7

12%

Article Metrics

Tooltip
Mentions
Blog Mentions: 1

Save time finding and organizing research with Mendeley

Sign up for free