Mutation in IL36RN impairs the processing and regulatory function of the interleukin-36-receptor antagonist and is associated with DITRA syndrome.
IL-36RN
IL-36Ra processing
generalized pustular psoriasis
inflammation
Journal
Experimental dermatology
ISSN: 1600-0625
Titre abrégé: Exp Dermatol
Pays: Denmark
ID NLM: 9301549
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
accepted:
04
05
2017
pubmed:
13
6
2017
medline:
12
9
2020
entrez:
13
6
2017
Statut:
ppublish
Résumé
The identification of loss-of-function mutations of the IL36RN gene encoding the interleukin-36 receptor antagonist (IL-36Ra) in generalized pustular psoriasis (GPP) emphasized the key role of this pathway in skin innate immunity and systemic inflammation. It has been previously shown in vitro that removal of the N-terminal amino acid IL36Ra (M1) is critical to its biological activity, but the in vivo contribution of this processing remains unknown. We report herein a new homozygous (c4G>T, pV2F) missense IL36RN mutation segregating in a family with three GPP-affected patients. The V2F mutation does not alter IL-36Ra protein expression but was devoid of any antagonist activity. Mass spectrometry showed that the V2F IL-36Ra mutant retains its first N-terminal methionine. These results provide the first in vivo demonstration that removal of N-terminal methionine of native IL-36Ra is a mandatory step to reach optimal antagonist activity and to prevent sustained skin and systemic inflammation in humans.
Substances chimiques
IL36RN protein, human
0
Interleukins
0
C-Reactive Protein
9007-41-4
Types de publication
Case Reports
Letter
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1114-1117Subventions
Organisme : SOCIETE FRANCAISE DE DERMATOLOGIE
Pays : International
Organisme : PHRC
Pays : International
Organisme : Amgen Inc.
Pays : International
Organisme : Pfizer
Pays : International
Informations de copyright
© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.