Universität zu Köln

Brunn, Anna, Mihelcic, Mirna ORCID: 0000-0002-8241-1721, Carstov, Mariana, Hummel, Lea, Geier, Frank, Schmidt, Annika, Saupe, Lisa, Utermoehlen, Olaf and Deckert, Martina (2014). IL-10, IL-4, and STAT6 Promote an M2 Milieu Required for Termination of PO106-125-Induced Murine Experimental Autoimmune Neuritis. Am. J. Pathol., 184 (10). S. 2627 - 2641. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1525-2191

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Abstract

The role of the type 2 helper T cell (Th2) polarizing cytokines IL-4 and IL-10 has not yet been studied in PO105-125-induced murine experimental autoimmune neuritis (EAN). We, therefore, addressed the functional relevance of these cytokines and signaling via the IL-4 associated transcription factor STAT6. The clinical course of PO106-125-induced EAN in mice deficient for IL-10(0/0), IL-4(0/0), or STAT6(0/0) was significantly aggravated compared with that of wild-type control mice. In addition, treatment of PO106-125-immunized C57BL/6 mice at the onset of clinical symptoms with a monoclonal IL-10 neutralizing antibody aggravated symptoms and prolonged disease to a similar degree as in IL-10(0/0) mice. This exacerbated course was attributed to a more prominent Th1 immune response associated with a persistent M1 milieu in the sciatic nerve and in the regional and systemic Lymphatic system. These data suggest a Th2-polarized milieu being required to prevent axonal damage of the sciatic nerve and to terminate the PO106-125-Specific immune response in EAN. Beyond the already known role of macrophages as pathogenic effector cells in EAN, these data suggest that M2-differentiated macrophages do not damage and may even protect neural tissues in EAN. Thus, these data highlight the pathogenetic relevance of the macrophage polarization status in EAN. Therapeutic modulation of immune responses from an M1 toward an M2 milieu may be a promising novel strategy in peripheral nervous system neuritis.

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 Hummel, Lea UNSPECIFIED UNSPECIFIED UNSPECIFIED Geier, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmidt, Annika UNSPECIFIED UNSPECIFIED UNSPECIFIED Saupe, Lisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Utermoehlen, Olaf UNSPECIFIED UNSPECIFIED UNSPECIFIED Deckert, Martina UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-427555
DOI:	10.1016/j.ajpath.2014.06.012
Journal or Publication Title:	Am. J. Pathol.
Volume:	184
Number:	10
Page Range:	S. 2627 - 2641
Date:	2014
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 PERIPHERAL NERVOUS-SYSTEM; GUILLAIN-BARRE-SYNDROME; EXPERIMENTAL ALLERGIC NEURITIS; CYTOKINE PRODUCTION; WALLERIAN DEGENERATION; ALTERNATIVE ACTIVATION; MESSENGER-RNA; NITRIC-OXIDE; T-CELLS; MACROPHAGES Multiple languages Pathology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42755