CCN3 is dynamically regulated by treatment and disease state in multiple sclerosis
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(2020) 17:349
RESEARCH
Open Access
CCN3 is dynamically regulated by treatment and disease state in multiple sclerosis Michelle Naughton1, Jill Moffat1, George Eleftheriadis1, Nira de la Vega Gallardo1, Andrew Young1, John Falconer1, Kristen Hawkins2, Ben Pearson2, Bernard Perbal3, Andrew Hogan4, Paul Moynagh1,4, Sam Loveless5, Neil P. Robertson5, Bruno Gran6, Rachael Kee7, Stella Hughes7, Gavin McDonnell7, Owain Howell2 and Denise C. Fitzgerald1*
Abstract Background: Multiple sclerosis (MS) is an immune-mediated disease that damages myelin in the central nervous system (CNS). We investigated the profile of CCN3, a known regulator of immune function and a potential mediator of myelin regeneration, in multiple sclerosis in the context of disease state and disease-modifying treatment. Methods: CCN3 expression was analysed in plasma, immune cells, CSF and brain tissue of MS patient groups and control subjects by ELISA, western blot, qPCR, histology and in situ hybridization. Results: Plasma CCN3 levels were comparable between collective MS cohorts and controls but were significantly higher in progressive versus relapsing-remitting MS and between patients on interferon-β versus natalizumab. Higher body mass index was associated with higher CCN3 levels in controls as reported previously, but this correlation was absent in MS patients. A significant positive correlation was found between CCN3 levels in matched plasma and CSF of MS patients which was absent in a comparator group of idiopathic intracranial hypertension patients. PBMCs and CD4+ T cells significantly upregulated CCN3 mRNA in MS patients versus controls. In the CNS, CCN3 was detected in neurons, astrocytes and blood vessels. Although overall levels of area immunoreactivity were comparable between non-affected, demyelinated and remyelinated tissue, the profile of expression varied dramatically. Conclusions: This investigation provides the first comprehensive profile of CCN3 expression in MS and provides rationale to determine if CCN3 contributes to neuroimmunological functions in the CNS. Keywords: Multiple sclerosis, CCN3, Myelin, Plasma, CSF
* Correspondence: [email protected] 1 Wellcome-Wolfson Institute for Experimental Medicine, Queen’s University Belfast, 97 Lisburn Road, Belfast, Northern Ireland BT9 7BL, UK Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory r
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