Universität zu Köln

Androulidaki, Ariadne, Wachsmuth, Laurens, Polykratis, Apostolos ORCID: 0000-0001-6720-3302 and Pasparakis, Manolis ORCID: 0000-0002-9870-0966 (2018). Differential role of MyD88 and TRIF signaling in myeloid cells in the pathogenesis of autoimmune diabetes. PLoS One, 13 (3). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

Type 1 diabetes (T1D) is caused by the autoimmune destruction of the insulin-producing pancreatic beta cells. While the role of adaptive immunity has been extensively studied, the role of innate immune responses and particularly of Toll-like Receptor (TLR) signaling in T1D remains poorly understood. Here we show that myeloid cell-specific MyD88 deficiency considerably protected mice from the development of streptozotocin (STZ)-induced diabetes. The protective effect of MyD88 deficiency correlated with increased expression of the immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) in pancreatic lymph nodes from STZ-treated mice and in bone marrow-derived dendritic cells (BMDC) stimulated with apoptotic cells. Mice with myeloid cell specific TIR-domain-containing adapter-inducing interferon-beta (TRIF) knockout showed a trend towards accelerated onset of STZ-induced diabetes, while TRIF deficiency resulted in reduced IDO expression in vivo and in vitro. Moreover, myeloid cell specific MyD88 deficiency delayed the onset of diabetes in Non-Obese Diabetic (NOD) mice, whereas TRIF deficiency had no effect. Taken together, these results identify MyD88 signaling in myeloid cells as a critical pathogenic factor in autoimmune diabetes, which is antagonized by TRIF-dependent responses. This differential function of MyD88 and TRIF depends at least in part on their opposite effects in regulating IDO expression in phagocytes exposed to apoptotic cells.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Androulidaki, Ariadne UNSPECIFIED UNSPECIFIED UNSPECIFIED Wachsmuth, Laurens UNSPECIFIED UNSPECIFIED UNSPECIFIED Polykratis, Apostolos UNSPECIFIED orcid.org/0000-0001-6720-3302 UNSPECIFIED Pasparakis, Manolis UNSPECIFIED orcid.org/0000-0002-9870-0966 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-192901
DOI:	10.1371/journal.pone.0194048
Journal or Publication Title:	PLoS One
Volume:	13
Number:	3
Date:	2018
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TOLL-LIKE RECEPTORS; DENDRITIC CELLS; INDOLEAMINE 2,3-DIOXYGENASE; APOPTOTIC CELLS; INNATE IMMUNITY; BETA-CELLS; NOD MOUSE; MICE; INDUCTION; PATHWAY Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/19290