Universität zu Köln

Mufazalov, Ilgiz A., Andruszewski, David ORCID: 0000-0003-3645-1877, Schelmbauer, Carsten, Heink, Sylvia, Blanfeld, Michaela, Masri, Joumana, Tang, Yilang ORCID: 0000-0001-7560-8369, Schueler, Rebecca, Eich, Christina, Wunderlich, F. Thomas, Karbach, Susanne H., Bluestone, Jeffrey A., Korn, Thomas and Waisman, Ari (2020). Cutting Edge: IL-6-Driven Immune Dysregulation Is Strictly Dependent on IL-6R alpha-Chain Expression. J. Immunol., 204 (4). S. 747 - 752. BETHESDA: AMER ASSOC IMMUNOLOGISTS. ISSN 1550-6606

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Abstract

IL-6 binds to the IL-6R alpha-chain (IL-6R alpha) and signals via the signal transducer gp130. Recently, IL-6 was found to also bind to the cell surface glycoprotein CD5, which would then engage gp130 in the absence of IL-6R alpha. However, the biological relevance of this alternative pathway is under debate. In this study, we developed a mouse model, in which murine IL-6 is overexpressed in a CD11c-Cre-dependent manner. Transgenic mice developed a lethal immune dysregulation syndrome with increased numbers of Ly-6G(+) neutrophils and Ly-6C(hi) monocytes/macrophages. IL-6 overexpression promoted activation of CD4(+) T cells while suppressing CD5(+) B-1a cell development. However, additional ablation of IL-6R alpha protected IL-6-overexpressing mice from IL-6-triggered inflammation and fully phenocopied IL-6R alpha-deficient mice without IL-6 overexpression. Mechanistically, IL-6R alpha deficiency completely prevented downstream activation of STAT3 in response to IL-6. Altogether, our data clarify that IL-6R alpha is the only biologically relevant receptor for IL-6 in mice.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Mufazalov, Ilgiz A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Andruszewski, David UNSPECIFIED orcid.org/0000-0003-3645-1877 UNSPECIFIED Schelmbauer, Carsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Heink, Sylvia UNSPECIFIED UNSPECIFIED UNSPECIFIED Blanfeld, Michaela UNSPECIFIED UNSPECIFIED UNSPECIFIED Masri, Joumana UNSPECIFIED UNSPECIFIED UNSPECIFIED Tang, Yilang UNSPECIFIED orcid.org/0000-0001-7560-8369 UNSPECIFIED Schueler, Rebecca UNSPECIFIED UNSPECIFIED UNSPECIFIED Eich, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Wunderlich, F. Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Karbach, Susanne H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bluestone, Jeffrey A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Korn, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Waisman, Ari UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-344786
DOI:	10.4049/jimmunol.1900876
Journal or Publication Title:	J. Immunol.
Volume:	204
Number:	4
Page Range:	S. 747 - 752
Date:	2020
Publisher:	AMER ASSOC IMMUNOLOGISTS
Place of Publication:	BETHESDA
ISSN:	1550-6606
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INTERLEUKIN-6; CELLS; CYTOKINES; RECEPTOR; GROWTH Multiple languages Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/34478