IL-38 Ameliorates Skin Inflammation and Limits IL-17 Production from γδ T Cells.
Animals
Antibodies
/ immunology
Cell Differentiation
Cytokines
/ metabolism
Disease Models, Animal
Humans
Imiquimod
/ toxicity
Inflammation
/ prevention & control
Interleukin-1
/ genetics
Interleukin-1 Receptor Accessory Protein
/ deficiency
Interleukin-17
/ metabolism
Keratinocytes
/ cytology
Mice
Mice, Inbred C57BL
Mice, Knockout
Psoriasis
/ chemically induced
Receptors, Antigen, T-Cell, gamma-delta
/ immunology
Regeneration
/ drug effects
Skin
/ metabolism
T-Lymphocytes
/ cytology
IL-17
IL-38
IL1RAPL1
inflammation
psoriasis
γδ T cells
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
16 04 2019
16 04 2019
Historique:
received:
02
07
2018
revised:
04
03
2019
accepted:
21
03
2019
entrez:
18
4
2019
pubmed:
18
4
2019
medline:
17
6
2020
Statut:
ppublish
Résumé
Interleukin-38 (IL-38) is a cytokine of the IL-1 family with a role in chronic inflammation. However, its main cellular targets and receptors remain obscure. IL-38 is highly expressed in the skin and downregulated in psoriasis patients. We report an investigation in cellular targets of IL-38 during the progression of imiquimod-induced psoriasis. In this model, IL-38 knockout (IL-38 KO) mice show delayed disease resolution with exacerbated IL-17-mediated inflammation, which is reversed by the administration of mature IL-38 or γδ T cell-receptor-blocking antibodies. Mechanistically, X-linked IL-1 receptor accessory protein-like 1 (IL1RAPL1) is upregulated upon γδ T cell activation to feedforward-amplify IL-17 production and is required for IL-38 to suppress γδ T cell IL-17 production. Accordingly, psoriatic IL1RAPL1 KO mice show reduced inflammation and IL-17 production by γδ T cells. Our findings indicate a role for IL-38 in the regulation of γδ T cell activation through IL1RAPL1, with consequences for auto-inflammatory disease.
Identifiants
pubmed: 30995480
pii: S2211-1247(19)30421-8
doi: 10.1016/j.celrep.2019.03.082
pii:
doi:
Substances chimiques
Antibodies
0
Cytokines
0
Il1f10 protein, mouse
0
Interleukin-1
0
Interleukin-1 Receptor Accessory Protein
0
Interleukin-17
0
Receptors, Antigen, T-Cell, gamma-delta
0
interleukin-1 receptor accessory protein-like 1, mouse
0
Imiquimod
P1QW714R7M
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
835-846.e5Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.