Format

Send to

Choose Destination
Cell Rep. 2019 Apr 16;27(3):835-846.e5. doi: 10.1016/j.celrep.2019.03.082.

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

Author information

1
Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany; Special Key Laboratory of Oral Diseases Research, Higher Education Institutions of Guizhou Province, Zunyi Medical University, 563006 Zunyi, Guizhou, China; School of Stomatology, Zunyi Medical University, 563006 Zunyi, Guizhou, China.
2
Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany; Faculty of Microbiology, University of Costa Rica, 2060 San José, Costa Rica.
3
Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany.
4
Institute of Clinical Pharmacology, Pharmazentrum Frankfurt/ZAFES, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt am Main, Germany; Branch for Translational Medicine and Pharmacology TMP, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, 60590 Frankfurt, Germany.
5
Branch for Translational Medicine and Pharmacology TMP, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, 60590 Frankfurt, Germany.
6
Institute of Molecular Cell Biology, Center for Molecular Biomedicine (CMB), Jena University Hospital, 07745 Jena, Germany.
7
Division of Rheumatology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.
8
Institut Cochin, Institut National de la Santé et de la Recherche Médicale U1016, Centre National de la Recherche Scientifique UMR8104, Université Paris Descartes, Paris 75014, France.
9
National Research Council Neuroscience Institute, 20129 Milan, Italy; Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, 20129 Milan, Italy.
10
Branch for Translational Medicine and Pharmacology TMP, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, 60590 Frankfurt, Germany; Division of Rheumatology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.
11
Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany; Branch for Translational Medicine and Pharmacology TMP, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, 60590 Frankfurt, Germany.
12
Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany. Electronic address: weigert@biochem.uni-frankfurt.de.

Abstract

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.

KEYWORDS:

IL-17; IL-38; IL1RAPL1; inflammation; psoriasis; γδ T cells

PMID:
30995480
DOI:
10.1016/j.celrep.2019.03.082
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center