Universität zu Köln

Brunn, A., Utermoehlen, O., Mihelcic, M., Sanchez-Ruiz, M., Carstov, M., Blau, T., Ustinova, I., Penfold, M., Montesinos-Rongen, M. and Deckert, M. (2013). Differential effects of CXCR4-CXCL12-and CXCR7-CXCL12-mediated immune reactions on murine P0(106-125)-induced experimental autoimmune neuritis. Neuropathol. Appl. Neurobiol., 39 (7). S. 772 - 788. HOBOKEN: WILEY. ISSN 1365-2990

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Abstract

Aim: The role of chemokines and their receptors, which regulate trafficking and homing of leucocytes to inflamed organs in human or murine autoimmune neuritis, has not yet been elucidated in detail, Therefore, the role of the chemokine receptors CXCR4 and CXCR7 and their ligand CXCL12 was studied in autoimmune-mediated inflammation of the peripheral nervous system. Methods: CXCL12/CXCR4 and/or CXCL12/CXCR7 interactions were specifically inhibited by the compounds AMD3100 or CCX771, respectively, in experimental autoimmune neuritis (EAN) of C57BL/6J mice immunized with P0(106-125) peptide. Results: Disease activity was significantly suppressed by blocking CXCR7 while antagonization of CXCR4 enhanced disease activity. Enhanced disease activity was accompanied by significantly increased transcription of IFN-gamma, IL-12 and TNF-alpha mRNA in regional lymph nodes and spleen as well as by increased serumlevels of IFN-gamma. Furthermore, by blocking CXCR4, expression of the cell adhesion molecules ICAM-1 and VCAM-1 was upregulated on vascular endothelial cells of the sciatic nerve, which coincided with significantly increased infiltration of the sciatic nerve by CD4+ T cells and macrophages. Remarkably, combined antagonization of both CXCR4 and CXCR7 significantly suppressed disease activity. This was accompanied by increased frequencies of activated and highly IFN-gamma-expressing, P0(106-125)-specific T cells in regional lymph nodes and spleen; however, these cells were unable to infiltrate the sciatic nerve. Conclusion: These data suggest differential and hierarchically ordered roles for CXCR4/CXCL12-vs. CXCR7/CXCL12-dependent effects during EAN: CXCR7/CXCL12 interaction is a gatekeeper for pathogenic cells, regardless of their CXCR4/CXCL12-dependent state of activation.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Brunn, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Utermoehlen, O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mihelcic, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sanchez-Ruiz, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Carstov, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Blau, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ustinova, I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Penfold, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Montesinos-Rongen, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Deckert, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-470371
DOI:	10.1111/nan.12039
Journal or Publication Title:	Neuropathol. Appl. Neurobiol.
Volume:	39
Number:	7
Page Range:	S. 772 - 788
Date:	2013
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1365-2990
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EXPERIMENTAL ALLERGIC NEURITIS; CHEMOKINE RECEPTOR; FACTOR-I; SELECTIVE EXPRESSION; ENDOTHELIAL-CELLS; NITRIC-OXIDE; T-CELLS; ADHESION; AMD3100; CXCL12 Multiple languages Clinical Neurology; Neurosciences; Pathology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47037