IL-38 Ameliorates Skin Inflammation and Limits IL-17 Production from γδ T Cells.

Authors:
Yingying Han
Yingying Han
University of Shanghai for Science and Technology
China
Javier Mora
Javier Mora
Institute of Biochemistry I
Germany
Svenja Wiechmann
Svenja Wiechmann
Goethe University School of Medicine
Frankfurt | Germany
Mateusz Putyrski
Mateusz Putyrski
Institute of Microbiology
Poland
Christian Schuster
Christian Schuster
Medical University of Graz
Austria
Eiman Elwakeel
Eiman Elwakeel
Research Institute
United States

Cell Rep 2019 Apr;27(3):835-846.e5

Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany. Electronic address:

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.

Download full-text PDF

Source
https://linkinghub.elsevier.com/retrieve/pii/S22111247193042
Publisher Site
http://dx.doi.org/10.1016/j.celrep.2019.03.082DOI Listing
April 2019
3 Reads

Publication Analysis

Top Keywords

il-17 production
16
γδ t cell
12
il-38
9
cellular targets
8
t cell activation
8
production γδ
8
γδ
6
il-38 progression
4
activation feedforward-amplify
4
progression imiquimod-induced
4
imiquimod-induced psoriasis
4
knockout il-38
4
il-38 knockout
4
model il-38
4
psoriasis model
4
feedforward-amplify il-17
4
investigation cellular
4
psoriasis patients
4
il-38 suppress
4
downregulated psoriasis
4

Altmetric Statistics

Similar Publications