Universität zu Köln

Steinhagen, Folkert, Zillinger, Thomas ORCID: 0000-0002-0866-4835, Peukert, Konrad, Fox, Mario, Thudium, Marcus ORCID: 0000-0002-9881-4875, Barchet, Winfried ORCID: 0000-0002-6745-6606, Putensen, Christian, Klinman, Dennis, Latz, Eicke ORCID: 0000-0003-1488-5666 and Bode, Christian ORCID: 0000-0002-0830-870X (2018). Suppressive oligodeoxynucleotides containing TTAGGG motifs inhibit cGAS activation in human monocytes. Eur. J. Immunol., 48 (4). S. 605 - 612. HOBOKEN: WILEY. ISSN 1521-4141

Full text not available from this repository.

Abstract

Type I interferon (IFN) is a critical mediator of autoimmune diseases such as systemic lupus erythematosus (SLE) and Aicardi-Goutieres Syndrome (AGS). The recently discovered cyclic-GMP-AMP (cGAMP) synthase (cGAS) induces the production of type I IFN in response to cytosolic DNA and is potentially linked to SLE and AGS. Suppressive oligodeoxynucleotides (ODN) containing repetitive TTAGGG motifs present in mammalian telomeres have proven useful in the treatment of autoimmune diseases including SLE. In this study, we demonstrate that the suppressive ODN A151 effectively inhibits activation of cGAS in response to cytosolic DNA, thereby inhibiting type I IFN production by human monocytes. In addition, A151 abrogated cGAS activation in response to endogenous accumulation of DNA using TREX1-deficient monocytes. We demonstrate that A151 prevents cGAS activation in a manner that is competitive with DNA. This suppressive activity of A151 was dependent on both telomeric sequence and phosphorothioate backbone. To our knowledge this report presents the first cGAS inhibitor capable of blocking self-DNA. Collectively, these findings might lead to the development of new therapeutics against IFN-driven pathologies due to cGAS activation.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Steinhagen, Folkert UNSPECIFIED UNSPECIFIED UNSPECIFIED Zillinger, Thomas UNSPECIFIED orcid.org/0000-0002-0866-4835 UNSPECIFIED Peukert, Konrad UNSPECIFIED UNSPECIFIED UNSPECIFIED Fox, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED Thudium, Marcus UNSPECIFIED orcid.org/0000-0002-9881-4875 UNSPECIFIED Barchet, Winfried UNSPECIFIED orcid.org/0000-0002-6745-6606 UNSPECIFIED Putensen, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Klinman, Dennis UNSPECIFIED UNSPECIFIED UNSPECIFIED Latz, Eicke UNSPECIFIED orcid.org/0000-0003-1488-5666 UNSPECIFIED Bode, Christian UNSPECIFIED orcid.org/0000-0002-0830-870X UNSPECIFIED
URN:	urn:nbn:de:hbz:38-190972
DOI:	10.1002/eji.201747338
Journal or Publication Title:	Eur. J. Immunol.
Volume:	48
Number:	4
Page Range:	S. 605 - 612
Date:	2018
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1521-4141
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GMP-AMP SYNTHASE; DNA SENSOR CGAS; MITOCHONDRIAL-DNA; INTERFERON RESPONSE; CELLS; TREX1; PATHWAY; DISEASE; IMMUNITY; PREVENT Multiple languages Immunology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/19097