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Journal of Neuroinflammation

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Open Access 01-12-2016 | Research

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

Authors: Alison McColl, Carolyn A. Thomson, Louis Nerurkar, Gerard J. Graham, Jonathan Cavanagh

Published in: Journal of Neuroinflammation | Issue 1/2016

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.

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Title: TLR7-mediated skin inflammation remotely triggers chemokine expression and leukocyte accumulation in the brain
Authors: Alison McColl
Carolyn A. Thomson
Louis Nerurkar
Gerard J. Graham
Jonathan Cavanagh
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2016
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-016-0562-2

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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