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Il-38 Restricts Skin Inflammation and Anti-Tumor Immunity by Limiting Il-17 Production from γδ T Cells

49 Pages Posted: 16 Jul 2018 Publication Status: Published

See all articles by Yingying Han

Yingying Han

Goethe University Frankfurt - Institute of Biochemistry I

Javier Mora

Goethe University Frankfurt - Institute of Biochemistry I

Mateusz Putyrski

Fraunhofer Institute for Molecular Biology and Applied Ecology - Branch for Translational Medicine and Pharmacology (TMP)

Arnaud Huard

Goethe University Frankfurt - Institute of Biochemistry I

Priscila da Silva

Goethe University Frankfurt - Institute of Biochemistry I

Anica Scholz

Goethe University Frankfurt - Institute of Biochemistry I

Eiman Elwakeel

Goethe University Frankfurt - Institute of Biochemistry I

Guangping Lang

Friedrich-Schiller-Universität Jena - Institute of Molecular Cell Biology

Tatjana Scholz

Goethe University Frankfurt - Division of Rheumatology

Tobias Schmid

Goethe University Frankfurt - Institute of Biochemistry I

Natasja de Bruin

Fraunhofer Institute for Molecular Biology and Applied Ecology - Branch for Translational Medicine and Pharmacology (TMP)

Pierre Billuart

Universite Paris Descartes - Institut Cochin

Carlo Sala

University of Milan - Department of Medical Biotechnology and Translational Medicine

Harald Burkhardt

Fraunhofer Institute for Molecular Biology and Applied Ecology - Branch for Translational Medicine and Pharmacology (TMP)

Michael J. Parnham

Fraunhofer Institute for Molecular Biology and Applied Ecology - Branch for Translational Medicine and Pharmacology (TMP)

Andreas Ernst

Fraunhofer Institute for Molecular Biology and Applied Ecology - Branch for Translational Medicine and Pharmacology (TMP)

Bernhard Brüne

Goethe University Frankfurt - Institute of Biochemistry I

Andreas Weigert

Goethe University Frankfurt - Institute of Biochemistry I

More...

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 receptor(s) remain obscure. IL-38 is highly expressed in the skin and downregulated in psoriasis patients. Therefore, we investigated cellular targets of IL-38 during the progression of imiquimod-induced psoriasis. In this model, IL-38-knockout (IL-38 KO) mice showed delayed disease resolution due to exacerbated IL-17-mediated inflammation, which was reversed by administration of mature IL-38. Mechanistically, IL-38 antagonized X-linked interleukin-1 receptor accessory protein-like 1 (IL1RAPL1), which was upregulated upon γδ T cell activation to feed-forward amplify IL-17 production. Heightened activation of tumor-infiltrating γδ T cells was also observed in IL-38 KO oncogene-driven mammary carcinoma, accompanied by attenuated tumor growth. Our findings, which are supported by clinical data, highlight the connection between auto-inflammation and anti-tumor immunity and indicate IL-38 as a potential therapeutic target under these conditions.

Suggested Citation

Han, Yingying and Mora, Javier and Putyrski, Mateusz and Huard, Arnaud and da Silva, Priscila and Scholz, Anica and Elwakeel, Eiman and Lang, Guangping and Scholz, Tatjana and Schmid, Tobias and de Bruin, Natasja and Billuart, Pierre and Sala, Carlo and Burkhardt, Harald and Parnham, Michael J. and Ernst, Andreas and Brüne, Bernhard and Weigert, Andreas, Il-38 Restricts Skin Inflammation and Anti-Tumor Immunity by Limiting Il-17 Production from γδ T Cells (2018). Available at SSRN: https://ssrn.com/abstract=3213912 or http://dx.doi.org/10.2139/ssrn.3213912
This version of the paper has not been formally peer reviewed.

Yingying Han

Goethe University Frankfurt - Institute of Biochemistry I

Germany

Javier Mora

Goethe University Frankfurt - Institute of Biochemistry I

Germany

Mateusz Putyrski

Fraunhofer Institute for Molecular Biology and Applied Ecology - Branch for Translational Medicine and Pharmacology (TMP)

Germany

Arnaud Huard

Goethe University Frankfurt - Institute of Biochemistry I

Germany

Priscila Da Silva

Goethe University Frankfurt - Institute of Biochemistry I

Germany

Anica Scholz

Goethe University Frankfurt - Institute of Biochemistry I

Germany

Eiman Elwakeel

Goethe University Frankfurt - Institute of Biochemistry I

Germany

Guangping Lang

Friedrich-Schiller-Universität Jena - Institute of Molecular Cell Biology

Germany

Tatjana Scholz

Goethe University Frankfurt - Division of Rheumatology

Germany

Tobias Schmid

Goethe University Frankfurt - Institute of Biochemistry I

Germany

Natasja De Bruin

Fraunhofer Institute for Molecular Biology and Applied Ecology - Branch for Translational Medicine and Pharmacology (TMP)

Germany

Pierre Billuart

Universite Paris Descartes - Institut Cochin

France

Carlo Sala

University of Milan - Department of Medical Biotechnology and Translational Medicine

Italy

Harald Burkhardt

Fraunhofer Institute for Molecular Biology and Applied Ecology - Branch for Translational Medicine and Pharmacology (TMP)

Germany

Michael J. Parnham

Fraunhofer Institute for Molecular Biology and Applied Ecology - Branch for Translational Medicine and Pharmacology (TMP)

Germany

Andreas Ernst

Fraunhofer Institute for Molecular Biology and Applied Ecology - Branch for Translational Medicine and Pharmacology (TMP)

Germany

Bernhard Brüne

Goethe University Frankfurt - Institute of Biochemistry I

Germany

Andreas Weigert (Contact Author)

Goethe University Frankfurt - Institute of Biochemistry I ( email )

Germany

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