TLR7-mediated skin inflammation remotely triggers chemokine expression and leukocyte accumulation in the brain

Mccoll, A., Thomson, C. A., Nerurkar, L., Graham, G. J. and Cavanagh, J. (2016) TLR7-mediated skin inflammation remotely triggers chemokine expression and leukocyte accumulation in the brain. Journal of Neuroinflammation, 13, 102. (doi: 10.1186/s12974-016-0562-2) (PMID:27160148)

[img]
Preview
Text
118636.pdf - Published Version
Available under License Creative Commons Attribution.

3MB

Abstract

Background: The relationship between the brain and the immune system has become increasingly topical as, although it is immune-specialised, the CNS is not free from the influences of the immune system. Recent data indicate that peripheral immune stimulation can significantly affect the CNS. But the mechanisms underpinning this relationship remain unclear. The standard approach to understanding this relationship has relied on systemic immune activation using bacterial components, finding that immune mediators, such as cytokines, can have a significant effect on brain function and behaviour. More rarely have studies used disease models that are representative of human disorders. Methods: Here we use a well-characterised animal model of psoriasis-like skin inflammation—imiquimod—to investigate the effects of tissue-specific peripheral inflammation on the brain. We used full genome array, flow cytometry analysis of immune cell infiltration, doublecortin staining for neural precursor cells and a behavioural read-out exploiting natural burrowing behaviour. Results: We found that a number of genes are upregulated in the brain following treatment, amongst which is a subset of inflammatory chemokines (CCL3, CCL5, CCL9, CXCL10, CXCL13, CXCL16 and CCR5). Strikingly, this model induced the infiltration of a number of immune cell subsets into the brain parenchyma, including T cells, NK cells and myeloid cells, along with a reduction in neurogenesis and a suppression of burrowing activity. Conclusions: These findings demonstrate that cutaneous, peripheral immune stimulation is associated with significant leukocyte infiltration into the brain and suggest that chemokines may be amongst the key mediators driving this response.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Thomson, Miss Carolyn and Cavanagh, Professor Jonathan and McColl, Dr Alison and Graham, Professor Gerard
Authors: Mccoll, A., Thomson, C. A., Nerurkar, L., Graham, G. J., and Cavanagh, J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Mental Health and Wellbeing
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Neuroinflammation
Publisher:BioMed Central Ltd
ISSN:1742-2094
ISSN (Online):1742-2094
Published Online:09 May 2016
Copyright Holders:Copyright © 2016 McColl et al.
First Published:First published in Journal of Neuroinflammation 13: 102
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record