Universität zu Köln

Brunn, Anna, Mihelcic, Mirna ORCID: 0000-0002-8241-1721, Carstov, Mariana, Feind, Lisa, Wieser, Eva C., Schmidt, Julia, Utermoehlen, Olaf and Deckert, Martina (2017). Toll-Like Receptor 2, Toll-Like Receptor 4, Myeloid Differentiation Response Gene 88, and Toll-IL-1 Receptor Domain-Containing Adaptor-Inducing Interferon-gamma (TRIF) Selectively Regulate Susceptibility of PO106-125-Induced Murine Experimental Autoimmune Neuritis. Am. J. Pathol., 187 (1). S. 42 - 55. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1525-2191

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Abstract

The functional relevance of the innate immune system has not yet been dissected in PO106-125-induced murine experimental autoimmune neuritis. Therefore, the role of Toll-like receptor (TLR) 2, TLR4, myeloid differentiation response gene 88, and ToLL IL-1 receptor domain-containing adaptor-inducing interferon-i (TRIF), factors critically involved in the TLR signaling pathway, was studied in experimental autoimmune neuritis. In the absence of TLR2, TLR4, myeloid differentiation response gene 88, or TRIF, the clinical course was significantly attenuated compared to wild-type mice. This could be attributed to impaired NE-kappa B activation, as shown by the absence of nuclear translocation of ReIA with a decreased expression of IL-6, IL 12p40, and IL-17A. Remarkably, PO106-125-immunized TLR2(0/0) mice exhibited a delayed recovery as compared to TLR4(0/0) mice, which was because of an impaired T helper cell 2 polarization. Immunized TLR2(0/0) mice' were unable to induce OX40 and OX4OL by matrix metalloproteinase-2 on spLenic dendritic cells. Subsequently, M2 polarization was impaired and macrophages were unable to sufficiently induce T regulatory cells (T-regs). Thus, in the recovery phase, Tregs were significantly increased in TLR4(0/0) mice as compared to wild-type mice, whereas T-regs in immunized TLR2(0/0) mice were only slightly increased. Our data highlight the relevance of innate immunity and, especially, the tight interaction between the innate and the adaptive immune system, which should be considered for therapeutic approaches of autoimmune diseases.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Brunn, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Mihelcic, Mirna UNSPECIFIED orcid.org/0000-0002-8241-1721 UNSPECIFIED Carstov, Mariana UNSPECIFIED UNSPECIFIED UNSPECIFIED Feind, Lisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Wieser, Eva C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmidt, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Utermoehlen, Olaf UNSPECIFIED UNSPECIFIED UNSPECIFIED Deckert, Martina UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-248123
DOI:	10.1016/j.ajpath.2016.09.009
Journal or Publication Title:	Am. J. Pathol.
Volume:	187
Number:	1
Page Range:	S. 42 - 55
Date:	2017
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1525-2191
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GUILLAIN-BARRE-SYNDROME; NF-KAPPA-B; T-CELLS; DENDRITIC CELLS; CUTTING EDGE; IN-VIVO; ACTIVATION; IMMUNITY; MICE; PATHWAY Multiple languages Pathology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/24812