The University of Southampton
Biological Sciences

Research project: Role of antibody-mediated immune responses in the CNS

Currently Active: 
Yes

We have made exciting and interesting observations on antibody mediated responses in the CNS which are particularly relevant for novel immunotherapeutic strategies to treat neurodegenerative diseases (Alzheimer’s disease) or autoimmune diseases (lupus and MS).

Project Overview

Using the classic Arthus reaction we found that immune complexes can be formed in the brain, which result in a delayed inflammatory reaction coinciding with an increase in Fc g receptors. We also explored the role of immune-regulatory receptors, including Fc g receptors, in a mouse model of chronic neurodegeneration and found them to be differentially up-regulated in the CNS during disease. These findings are novel and suggest that the immune system and in particular, antibodies and their receptors, might have a role in neurological diseases. The balance of activating and inhibiting Fc g receptors and their associated signaling pathways, ITAM vs ITIM, are critical in maintaining immune homeostasis, a subject which has been overlooked in the brain and neurodegeneration. Investigation of Fc g receptor expression levels, their signaling pathways, and their down stream effects are therefore crucial to understand the consequences of antibody mediated immune responses in the CNS.

Approaches:

We use a range of biochemical and molecular biology techniques to explore changes in protein and gene expression. The core facilities of the School of Biological sciences, including the confocal microscopy suite and the proteomics facility provide the necessary tools and expertise to study expression levels at a cellular level. The observations made at genomic and protein level are translated to whole system biology using appropriate animal models, including those for acute and chronic neurodegeneration (i.e., prion disease) and autoimmune diseases (multiple sclerosis and lupus).

Collaborations:

To support our projects, we work in close collaboration with members of the CNS inflammation group, headed by Prof V. Hugh Perry and with collaborators in the School of Medicine (Prof Martin Glennie, Dr Mark Cragg, Dr Sonia Quaratino, Dr Roxana Carare, Prof James Nicoll, Prof. Robert Peveler). In addition we have started collaboration with Dr Tracy Melvin in the Optoelectronic Research Center (ORC), providing opportunities to develop novel technologies that will greatly benefit our understanding of neuro-inflammation. Collaborators outside the University include Prof Paul Crocker (University of Dundee), Prof Herald Neumann (University of Bonn, Germany), Prof Ron Taylor ( Virginia, USA), and Dr Elga de Vries ( Free University Medical Center, Amsterdam, The Netherlands).

Related research groups

Biomedical Sciences

Staff

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