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an investigation into the role of neurotransmitter receptors in the function of human immune cells

Milton, Sarah Elizabeth (2012)
Ph.D. thesis, University of Birmingham.

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Abstract

The interaction between the nervous and immune system is well documented, although is still not fully understood - particularly the impact of neurotransmitter receptors on immune cell function. 5-HT\(_3\)A receptor expression was identified on activated regulatory T cells (Treg) but not on effector T cells. Incubation of human peripheral blood mononuclear cells (PBMC) with the 5-HT\(_3\) receptor agonist DDP733 and the positive allosteric modulator 5-chloroindole increased the percentage of CD25+FoxP3+ lymphoyctes (Treg phenotype). Proliferation of PBMC was inhibited by DDP733 plus 5-chloroindole indicating functional impact by the 5-HT\(_3\) receptor. The GPR55 receptor was also expressed by human T cells. The GPR55 agonist lysophosphatidylinositol increased cell viability by preventing apoptosis. However, the induced response was not blocked by the GPR55 receptor antagonist cannabidiol casting doubt over the GPR55 receptor mediating the response. Cannabidiol was demonstrated to have a pro-apoptotic effect in its own right, although whether this effect is mediated by GPR55 or the CB2 cannabinoid receptor is unknown. Further experiments are required to elucidate the role of the 5-HT\(_3\)A receptor in lymphocyte function and the mechanism responsible for the immunoprotective role of lysophosphatidylinositol.

Type of Work:Ph.D. thesis.
Supervisor(s):Barnes, Nicholas and Gordon, John
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Clinical and Experimental Medicine, Department of Neuroscience
Subjects:QR180 Immunology
RC Internal medicine
Institution:University of Birmingham
ID Code:3435
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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